Guidance and navigation control (GNC) antibody-like proteins, and methods of making and using the same

Abstract

To provide: multi-specific antibody-like proteins; immuno-conjugates comprising a cytotoxic or imaging agent linked to the multi-specific antibody-like proteins; and pharmaceutical compositions.SOLUTION: The invention provides multi-specific antibody-like proteins with one or more binding domains including a first binding domain (D1), a second binding domain (D2), a third binding domain (D3), a fourth binding domain (D4), a fifth binding domain (D5) or a sixth binding domain (D6). The multi-specific antibody-like proteins may be mono-specific, bi-specific, tri-specific, tetra-specific, penta-specific or hexa-specific. Such binding domains as D1, D2, D3, D4, D5 and D6 each independently have a specific binding affinity to a T cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a co-stimulation factor, a receptor of a leukocyte, a tumor antigen, a tumor associated antigen (TAA), a receptor of a tissue cell, a receptor of a cancer cell, or a combination thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 62 / 991,042, filed March 17, 2020 (35 U.S.C. 119(e)), the entire disclosure of which is incorporated herein by reference.

[0003] This application relates to the technical field of multispecific antibodies for use in cancer immunotherapy, and more specifically to methods for making and using guidance and navigation control (GNC) antibodies that have multibinding activity for surface molecules on both immune cells and tumor cells. [Background technology]

[0004] Cancer cells employ various strategies to evade destruction and elimination by the host immune system. There is an urgent need to improve the function, specificity, potency, and efficacy of biologic therapies. The success of targeted therapies in cancer treatment has also been hindered by various resistance mechanisms. Tumor plasticity has emerged as a mode of targeted therapy evasion in a variety of cancers, from prostate and lung adenocarcinoma to melanoma and basal cell carcinoma. Mechanisms that prevent the formation of robust antitumor immune responses are thought to include at least some of the following categories: 1) defects in tumor antigen processing or presentation; 2) lack of activation mechanisms; 3) inhibitory mechanisms and immunosuppressive states; and 4) resistant tumor cells (4). To overcome these evasion and resistance mechanisms, new therapeutic strategies have been designed to facilitate combination immunotherapy strategies that utilize multiple immune effectors (including, but not limited to, T cell engagers, checkpoint inhibitors, and innate immunity). However, such combination strategies often involve two or more independent biologics, each of which requires clinical safety and efficacy approval, as well as the manufacturing of each independent biologic. Combination therapies may target either immune cells or tumor cells, or both. For example, antibody therapy uses bispecific antibodies targeting both CD3 and CD19, or CAR-T cell therapy involves engineered T cells expressing anti-CD19 chimeric antibodies. One common side effect of these immunotherapies is cytokine release syndrome, which indicates insufficient immune regulation. In this context, new strategies are needed to overcome tumor plasticity, i.e., the heterogeneous and dynamic expression of tumor antigens and / or resistant tumor cells, while also achieving additional immune regulation.

[0005] To this end, a multispecific antibody platform, also known as guidance and navigation control (GNC), has been established to facilitate the multiple targeting of T cell engagers, costimulators, checkpoint inhibitors, and tumor antigens (Applicant's applications WO / 2019 / 005641, WO2019191120, and PCT / US20 / 59230; incorporated herein in their entireties). Furthermore, tetraspecific GNC (tetra-GNC) antibodies can be used to construct GNC-T cell therapies for treating both liquid and solid tumors. Despite the multifunctional GNC molecule, epitope-negative tumor cells remain untargeted, thus evading immunotherapy. For example, NKG2D ligand expression is tightly regulated to prevent autoimmune tissue damage, and therefore normal tissues typically do not express NKG2D ligands. Therefore, using the NKG2D receptor could be an effective targeting mechanism for cancer immunotherapy via the innate immune recognition process. Therefore, there is a clear need for further development of multispecific antibodies relevant to cell therapy. Although multispecific monoagents remain highly desirable and cost-effective, it is technically challenging to design, express, and produce potent and stable multispecific antibodies beyond the tetra-GNC antibody. Summary of the Invention

[0006] The following summary is illustrative only and is not intended to be in any way limiting. In addition to the exemplary aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.

[0007] The present invention provides proteins with binding specificities (e.g., multispecific antibody-like proteins and fragments thereof), and methods for producing and using multispecific antibody-like proteins and fragments thereof. The multispecific antibody-like proteins may include multispecific antibodies. Fragments of these binding proteins may include, but are not limited to, scFv domains, Fab regions, Fc domains, VH, VL, light chains, heavy chains, variable regions, and complementarity-determining regions (CDRs).

[0008] In one embodiment, the multispecific antibody-like protein may be a multispecific antibody, a monoclonal antibody, an isolated monoclonal antibody, or a humanized antibody.

[0009] In one embodiment, the protein may comprise various domains and regions, such as binding domains. In one embodiment, the multispecific antibody-like protein may have one or more binding domains, including the first binding domain (D1), the second binding domain (D2), the third binding domain (D3), the fourth binding domain (D4), the fifth binding domain (D5), or the sixth binding domain (D6). The multispecific antibody-like proteins of the present invention may be monospecific, bispecific, trispecific, tetraspecific, pentaspecific, or hexaspecific.

[0010] In one embodiment, the binding domains, such as D1, D2, D3, D4, D5, and D6, may each independently have specific binding affinity for a T cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a costimulatory factor, a receptor on leukocytes, a tumor antigen, a tumor-associated antigen (TAA), a receptor on tissue cells, a receptor on cancer cells, or a combination thereof.

[0011] In one embodiment, the T cell activating receptor may include CD3. In one embodiment, the immune checkpoint receptor may include PD-L1, PD-1, TIGIT, TIM-3, LAG-3, CTLA4, BTLA, VISTA, PD-L2, CD160, LOX-1, Siglec-15, CD47, HVEM SIRPα, CSF1R, CD73, Siglec-15, CD47, or a combination thereof. In one embodiment, the costimulatory receptor may include 4-1BB, CD28, OX40, GITR, CD40L, CD40, ICOS, LIGHT, CD27, CD30, or a combination thereof. In one embodiment, the tumor-associated antigen may comprise EGFR, HER2, HER3, EGRFVIII, CD19, BCMA, CD20, CD33, CD123, CD22, CD30, ROR1, CEA, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, TROP2, NKG2D ligand, CD39, CLDN18.2, DLL3, HLA-G, FcRH5, GPRC5D, LIV-1, MUC1, CD138, CD70, uPAR, CD38, or a combination thereof.

[0012] In one embodiment, a binding domain for a T cell activating receptor is adjacent to a binding domain for a tumor-associated antigen (TAA).

[0013] In one embodiment, D1, D3, D4, D5, and D6 may each independently be an scFv domain, a receptor, or a ligand. In one embodiment, at least one, two, three, four, or five of D1, D3, D4, D5, and D6 in the hexabody-like protein comprise an scFv domain. In one embodiment, D1, D3, D4, D5, and D6 are all scFv domains.

[0014] In one embodiment, at least one, two, three, four or five of D1, D3, D4, D5 and D6 in the hexabody-like protein comprise a receptor. In one embodiment, D1, D3, D4, D5 and D6 are all receptors.

[0015] In one embodiment, at least one, two, three, four or five of D1, D3, D4, D5 and D6 in the hexabody-like protein comprise a ligand. In one embodiment, D1, D3, D4, D5 and D6 all comprise a ligand.

[0016] In one embodiment, the scFv domain may comprise a VH linked to a VL in a VH-VL or VL-VH orientation. In one embodiment, the scFv domain may comprise a disulfide bond between the VL and VH. In one embodiment, the disulfide bond is between VL100 and VH44 of the scFv domain. In one embodiment, the scFv domain may comprise the substitution R19S (Kabat) in the VH.

[0017] In one embodiment, the multispecific antibody-like protein may comprise an Fc region. In one embodiment, the Fc region is engineered to eliminate effector cell functions, including but not limited to, ADCC, ADCP, or CDC. In one embodiment, the Fc region comprises at least one mutation at L234A, L235A, G237A, or K322A (Eu numbering). In one embodiment, the Fc region comprises mutations at L234A / L235A / G237A / K322A. In one embodiment, the Fc region comprises mutations at L234A / L235A / K322A (Eu numbering).

[0018] The domains and regions can be connected via a linker. In one embodiment, the linker is x S y ) n wherein n, x, and y are each independently an integer from 1 to 10. In one embodiment, n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment, x is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In one embodiment, y is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0019] In one aspect, the present invention provides a hexa-specific antibody-like protein. In one embodiment, the hexa-specific antibody-like protein has an N-terminus and a C-terminus, and comprises, in tandem from N-terminus to C-terminus, a Fab region which may include a first binding domain (D1) at the N-terminus, a light chain as the second binding domain (D2), an Fc region, a third binding domain (D3) having binding affinity for PD-L1, and a fourth binding domain (D4) at the C-terminus having binding affinity for 4-1BB, wherein the light chain may comprise a fifth binding domain (D5) covalently linked to the C-terminus and a sixth binding domain (D6) covalently linked to the N-terminus. D1, D2, D5, and D6 may each independently have binding affinity for a tumor-associated antigen (TAA) or CD3.

[0020] In one embodiment, the hexa-specific antibody-like protein may comprise D1 or D2 having binding affinity for CD3. In one embodiment, the hexa-specific antibody-like protein may comprise D1 having binding affinity for CD3. In one embodiment, the hexa-specific antibody-like protein may comprise D2 having binding affinity for CD3.

[0021] In one embodiment, the hexaspecific antibody-like protein may comprise D1, which has binding specificity for CD3; D2, which has binding specificity for EGFR, EGFRvIII, CD20, mesothelin, claudin 18.2, HER2, CD33, or a combination thereof; D3, which has binding specificity for PD-L1; D4, which has binding specificity for 4-1BB; and D5 and D6, each independently having binding specificity for a tumor-associated antigen.

[0022] In one embodiment, the hexaspecific antibody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for a tumor-associated antigen; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; and D5 and D6, each independently having binding specificity for an NKG2D ligand, HER3, CD19, or a combination thereof.

[0023] In one embodiment, the hexaspecific antibody-like protein may comprise D1 having binding specificity for EGFR; D2 having binding specificity for CD3; D3, which may have binding specificity for PD-L1; D4 having binding specificity for 4-1BB; D5 having binding specificity for CD19; and D6 having binding specificity for HER3.

[0024] In one embodiment, the hexaspecific antibody-like protein may comprise D1 having binding specificity for EGFR; D2 having binding specificity for CD3; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; D5 having binding specificity for HER3; and D6 having binding specificity for CD19.

[0025] In one embodiment, the hexaspecific antibody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for EGFR; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; D5 having binding specificity for HER3; and D6 having binding specificity for CD19.

[0026] In one embodiment, the hexabody-like protein may comprise an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO: 176, 178, 106, 108, 332, 334, 324, 326, 328 or 330.

[0027] In one aspect, the present invention provides a tetraspecific or pentaspecific antibody-like protein. In one embodiment, the antibody-like protein comprises an N-terminus and a C-terminus, and may comprise, in tandem from N-terminus to C-terminus, a Fab region which may include a first binding domain (D1) at the N-terminus, a light chain as the second binding domain (D2) (which may optionally include a fifth binding domain (D5) covalently bound to the C-terminus or a sixth binding domain (D6) covalently bound to the N-terminus), an Fc region, a third binding domain (D3), and a fourth binding domain (D4) at the C-terminus. In one embodiment, the multispecific antibody-like protein is selected from the group consisting of SEQ ID NOs: 110, 112, 116, 118, 122, 124, 128, 130, 134, 136, 140, 142, 146, 148, 152, 154, 158, 160, 164, 166, 170, 172, 112, 114, 118, 120, 124, 126, 130, 132, 136, 138, 142, 144, 148, 150, 154, 156, 160, 162, 166, 168, 172, 174, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 302, 304, 306 or 308.

[0028] In one embodiment, the multispecific antibody-like protein may be tetraspecific. In one embodiment, the multispecific antibody-like protein may be pentaspecific. In one embodiment, D2, D5, and D6 may each independently have binding affinity for a tumor-associated antigen (TAA).

[0029] In one embodiment, the tetraspecific antibody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for a tumor-associated antigen; D3 having binding specificity for PD-L1; and D4 having binding specificity for 4-1BB.

[0030] In one embodiment, the tetraspecific antibody-like protein may comprise D1, which has binding specificity for CD3; D2, which has binding specificity for an antigen selected from the group consisting of EGFR, HER2, CD19, CD20, CD22, CD30, CD22, mesothelin, GD2, and claudin 18.2; D3, which has binding specificity for PD-L1; and D4, which has binding specificity for 4-1BB.

[0031] In one embodiment, the pentabody-like protein may comprise D1, which has binding specificity for CD3; D2 and D5, each independently having binding specificity for a tumor-associated antigen; D3, which has binding specificity for PD-L1; and D4, which has binding specificity for 4-1BB.

[0032] In one embodiment, the pentaspecific antibody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for a tumor-associated antigen; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; and D5 having binding specificity for HER3.

[0033] In one embodiment, the pentabody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for EGFR or EGFRvIII; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; and D5 having binding specificity for HER3.

[0034] In one embodiment, the pentaspecific antibody-like protein may comprise D1 having binding specificity for CD3; D2 having binding specificity for CD20; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; and D5 having binding specificity for CD19.

[0035] In one embodiment, the pentaspecific antibody-like protein may comprise D1 and D6, each independently having binding specificity for a tumor-associated antigen; D2 having binding specificity for CD3; D3 having binding specificity for PD-L1; and D4 having binding specificity for 4-1BB.

[0036] In one embodiment, the pentabody-like protein may comprise D1 having binding specificity for EGFR; D2 having binding specificity for CD3; D3 having binding specificity for PD-L1; D4 having binding specificity for 4-1BB; and D6 having binding specificity for CD19.

[0037] In one aspect, the present invention provides a multispecific antibody-like protein having at least one binding domain as a receptor, in one embodiment, said receptor is NKG2D.

[0038] In one embodiment, the multispecific antibody-like protein comprises an N-terminus and a C-terminus, and comprises, in tandem from N-terminus to C-terminus, a first binding domain (D1), optionally at the N-terminus, a second binding domain (D2), which may comprise a light chain (which may optionally include a fifth binding domain (D5) covalently linked to the C-terminus and / or a sixth binding domain (D6) covalently linked to the N-terminus), an Fc region, optionally a third binding domain (D3), and optionally a fourth binding domain (D4) at the C-terminus, wherein at least one of D1, D2, D3, D4, D5, and D6 is NKG2D, and D1, D2, D3, D4, D5, and D6 may each independently have binding affinity specific to a T-cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a costimulatory factor, a receptor on leukocytes, a tumor antigen, a tumor-associated antigen (TAA), a receptor on tissue cells, a receptor on cancer cells, or a combination thereof.

[0039] In one embodiment, the multispecific antibody-like protein comprising NKG2D can be monospecific, bispecific, trispecific, tetraspecific or pentaspecific.

[0040] In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise a D2 comprising a dimer linked to CL and CH1, wherein the dimer is NKG2D. In one embodiment, a monospecific antibody-like protein comprising NKG2D may comprise an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 196 or 198.

[0041] In one embodiment, the multispecific antibody-like protein comprising NKG2D is each independently selected from the group consisting of EGFR, HER2, HER3, EGFRvIII, ROR1, CD3, CD28, CEA, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, TROP2, NKG2D, NKG2D ligand, BCMA, CD19, CD20, CD33, CD123, CD22, CD30, PD-L1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, and LAG-3. , CTLA4, CD40, CD40L, VISTA, ICOS, BTLA, LIGHT, HVEM, CSF1R, CD73, CD39, CLDN18.2, DLL3, HLA-G, FcRH5, GPRC5D, LIV-1, MUC1, CD138, CD70, CD16, uPAR, Siglec-15, CD47, CD38, NKp46, PD-L2, CD160, LOX-1, SIRPα, and CD27. The Fc domain may comprise a human IgG Fc domain.

[0042] In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise D2, D5, and D6, each independently having binding specificity for a tumor-associated antigen. In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise D2, which has binding specificity for a tumor-associated antigen. In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise D1, D2, D3, and D4, each independently having binding specificity for an NKG2D ligand, CD3, PD-L1, 4-1BB, or a combination thereof.

[0043] In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise an amino acid sequence having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 78, 80, 82, 84, 86, 88, 30 or 32.

[0044] In one embodiment, a multispecific antibody-like protein comprising NKG2D may comprise D1 having binding specificity for an NKG2D ligand; D2 having binding specificity for CD3; D3 having binding specificity for PD-L1; and D4 having binding specificity for 4-1BB.

[0045] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for an NKG2D ligand; D2, which has binding specificity for CD3; D3, which has binding specificity for 4-1BB; and D4, which has binding specificity for PD-L1.

[0046] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for 4-1BB; D2, which has binding specificity for PD-L1; D3, which has binding specificity for CD3; and D4, which has binding specificity for an NKG2D ligand.

[0047] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for PD-L1; D2, which has binding specificity for 4-1BB; D3, which has binding specificity for CD3; and D4, which has binding specificity for an NKG2D ligand.

[0048] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for a tumor-associated antigen; D3, which has binding specificity for PD-L1; D4, which has binding specificity for 4-1BB; and D5, which has binding specificity for an NKG2D ligand.

[0049] In one embodiment, the multispecific antibody-like protein comprising NKG2D comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an antigen selected from the group consisting of mesothelin, claudin 18.2, HER2, EGFRvIII, and CD33; D3, which has binding specificity for PD-L1; D4, which has binding specificity for 4-1BB; and D5, which has binding specificity for an NKG2D ligand.

[0050] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; and D2, which has binding specificity for an NKG2D ligand.

[0051] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an NKG2D ligand; and D6, which has binding specificity for a tumor-associated antigen.

[0052] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an NKG2D ligand; and D6, which has binding specificity for CD19.

[0053] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an NKG2D ligand; D3, which has binding specificity for PD-L1; and D4, which has binding specificity for 4-1BB.

[0054] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an NKG2D ligand; D3, which has binding specificity for PD-L1; D4, which has binding specificity for 4-1BB; and D6, which has binding specificity for a tumor-associated antigen.

[0055] In one embodiment, the NKG2D-comprising multispecific antibody-like protein comprises D1, which has binding specificity for CD3; D2, which has binding specificity for an NKG2D ligand; D3, which has binding specificity for PD-L1; D4, which has binding specificity for 4-1BB; and D6, which has binding specificity for CD19.

[0056] In a second aspect, the present invention provides an isolated nucleic acid sequence encoding the amino acid sequence of a multispecific antibody-like protein of the present invention.

[0057] In a third aspect, the present invention provides an expression vector, hi one embodiment, the expression vector comprises an isolated nucleic acid sequence of the present invention.

[0058] In another aspect, the present invention provides a host cell comprising the isolated nucleic acid sequence. In one embodiment, the host cell is a prokaryotic cell. In one embodiment, the host cell is a eukaryotic cell.

[0059] In another aspect, the present invention provides multispecific antibody-like proteins and fragments thereof. In one embodiment, the method comprises culturing a host cell containing an isolated nucleic acid sequence such that a DNA sequence encoding the multispecific antibody or a monomer is expressed; and purifying the multispecific antibody. The isolated nucleic acid sequence encodes the amino acids of the multispecific antibody-like protein or fragment thereof.

[0060] In another aspect, the present invention provides an immunoconjugate. In one embodiment, the immunoconjugate may comprise a cytotoxic agent or imaging agent conjugated to the multispecific antibody via a linker. The linker may comprise an ester bond, an ether bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphate ester bond, a peptide bond, a hydrophobic poly(ethylene glycol) linker, or a combination thereof. In one embodiment, the cytotoxic agent or imaging agent may comprise a chemotherapeutic agent, a growth inhibitory agent, a cytotoxic agent from the calicheamicin class, a mitotic inhibitor, a radioisotope, a toxin, a therapeutic agent, or a combination thereof.

[0061] In another aspect, the present invention provides pharmaceutical compositions. In one embodiment, the pharmaceutical composition may comprise a pharmaceutically acceptable carrier and a multispecific antibody protein or fragment thereof, and / or an immunoconjugate. In one embodiment, the pharmaceutical composition may comprise a therapeutic agent selected from a radioisotope, a radionuclide, a toxin, a chemotherapeutic agent, or a combination thereof.

[0062] In another aspect, the present invention provides a method for treating or preventing cancer, an autoimmune disease, or an infectious disease in a subject. In one embodiment, the method comprises administering a pharmaceutical composition that may comprise a purified multispecific antibody-like protein or a fragment thereof. In one embodiment, the method may comprise administering to the subject an effective amount of the purified multispecific antibody-like protein, immunoconjugate, or pharmaceutical composition.

[0063] In one embodiment, the method may further comprise co-administering an effective amount of a therapeutic agent, including an antibody, a chemotherapeutic agent, an enzyme, an anti-estrogen, a receptor tyrosine kinase inhibitor, a kinase inhibitor, a cell cycle inhibitor, a checkpoint inhibitor, a DNA, RNA or protein synthesis inhibitor, a RAS inhibitor, an inhibitor of PD1, PD-L1, CTLA4, 4-1BB, OX40, GITR, ICOS, LIGHT, TIM3, LAG3, TIGIT, CD40, CD27, HVEM, BTLA, VISTA, B7H4, CSF1R, NKG2D, CD73, or a combination thereof.

[0064] In one embodiment, the subject is a human. In one embodiment, the subject is a mammal. In one embodiment, the subject is a chimpanzee. In one embodiment, the subject is a pet animal.

[0065] In another aspect, the present invention provides a solution comprising an effective amount of a purified multispecific antibody-like protein or fragment thereof, immunoconjugate, or pharmaceutical composition, hi one embodiment, the solution is plasma of a human subject. [Brief explanation of the drawings]

[0066] The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings, which illustrate only some embodiments prepared in accordance with the present disclosure and therefore should not be considered limiting of its scope, the present disclosure may be explained with additional specificity and detail through the use of the accompanying drawings.

[0067] [Figure 1] The present invention provides a hexaGNC antibody having a Fab region or dimeric receptor as the D2 binding domain, and five antigen-binding domains in the heavy chain (D1, D3, and D4) and light chain (D5 and D6), and having a variety of structures selected from antibody fragments based on variable sequences, receptors, and ligands encoded by non-variable sequences.

[0068] [Figure 2] Analytical SEC results demonstrating the stability and high quality of purified tetra-GNC antibody (A-C) containing NKG2D receptor and 41BBL, as well as purified NKG2D penta-GNC (D).

[0069] [Figure 3] Figure 1 shows a TDCC assay measuring the comparative potency of four tetra-GNC antibodies (SI-49E1, SI-49E2, SI-49E3, SI-49E4) and two bispecific control antibodies lacking both the αPD-L1 and α41BB domains (SI-49X1, SI-49X2) in targeting the MICA expressing MDA-MB-231 cell line.

[0070] [Figure 4] TDCC assay measuring the comparative potency of one NKG2D-MSLN penta-GNC (SI-49P1), two MSLN tetra-GNCs (SI-51E4 and SI-51E1), and one NKG2D-MSLN tri-GNC (SI-51X1, control) in targeting MICA- and mesothelin-expressing MDA-MB-231 cells.

[0071] [Figure 5] 1 shows a TDCC assay measuring the comparative potency of tetra-GNC antibodies with three moiety 1 binding domains and a single moiety 2 that specifically binds to a tumor antigen in targeting a group of cervical cancer cells (Hela).

[0072] [Figure 6] 1 shows a TDCC assay measuring the comparative potency of multispecific GNC antibodies with the same binding specificity for EGFR for all molecules and the same binding specificity for HER3 for SI-1 and SI-1P2 in targeting EGFR-expressing MDA-MB-231 breast cancer cells in the presence and absence of portion 1 binding specificity (SI-1) (SI-1P2, SI-55E1, and SI-55E2).

[0073] [Figure 7] TDCC assay measuring the comparative potency of tetra-GNC with (SI-50E6, stapled) and without (SI-50E1) additional disulfide bonds in all scFv domains compared to bi-GNC antibody (SI-50X1) in targeting EGFR-expressing MDA-MB-231 breast cancer cells.

[0074] [Figure 8] 1 shows the production of a class of multispecific GNC antibodies with any combination of three part 1 binding specificities against CD3, PD-L1, and 4-1BB from D1, D3, and D4, and part 2 binding specificities against three tumor antigens from D2, D5, and D6, by a modular cloning system. DETAILED DESCRIPTION OF THE INVENTION

[0075] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, like symbols generally identify like components unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that aspects of the present disclosure, as described herein and illustrated in the figures, can be arranged, substituted, combined, separated, and designed in various configurations expressly contemplated herein.

[0076] The present invention provides, inter alia, isolated antibodies, methods for making the antibodies; bispecific or multispecific molecules, antibody-drug conjugates and / or immunoconjugates composed of the antibodies or antigen-binding fragments; pharmaceutical compositions comprising the antibodies, bispecific or multispecific molecules, antibody-drug conjugates and / or immunoconjugates; methods for making the molecules and compositions; and methods for treating cancer using the molecules and compositions of the invention.

[0077] The present invention relates to methods for producing and using multispecific GNC antibodies, particularly tetraspecific, pentaspecific, and hexaspecific GNC (tetra-GNC, penta-GNC, hexa-GNC) antibodies. GNC proteins, such as GNC antibodies, are generally characterized by two moieties: moiety 1, which is involved in immune cell activation, such as T cell activation, and moiety 2, which targets tumor cells. GNC antibodies possess multiple antigen-binding domains involved in immune cell activation, such as anti-CD3 for T cell activation, anti-4-1BB for costimulation, and anti-PD-L1 for immune checkpoint inhibition. To improve the efficacy of antibody therapy for cancer treatment, GNC antibodies have been designed to be structurally stable and compact while retaining the characteristics of the two moieties of the GNC antibody. This improvement allows for additional binding specificity for a second tumor-associated antigen on the same or a different tumor cell. GNC antibodies contain an Fc domain, which allows for FcRn-mediated recycling, extended half-life, and easy protein A-based purification. If necessary, Fc receptor-mediated immunity can be incorporated. GNC antibodies are typically larger than IgG antibodies due to their expanded antigen-binding domain (AgBD), which provides spatial flexibility for binding to both T cells and tumor cells. GNC antibodies may be effective antibody therapies for treating cancer by targeting one or more tumor antigens (including, but not limited to, BCMA, CD19, CD20, CD33, CD123, CD22, CD30, ROR1, CEA, HER2, HER3, EGFR, EGFRvIII, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, and TROP2). Multispecific T cell-engaging antibodies, such as tetra- and penta-GNC antibodies, offer distinct advantages over conventional immunotherapies. These antibodies exhibit the ability to crosslink CD3 on T cells bearing tumor-associated antigens (TAA), allowing them to be redirected and directed to kill tumor cells without the need to remove the T cells from the patient or genetically modify them to be specific for tumor cells before being reintroduced into the patient (also known as chimeric antigen receptor T cell or CAR-T therapy).GNC protein-mediated antibody therapy or T cell therapy does not involve genetic modification of T cells, which may carry the risk of clonal proliferation of the modified T cells, i.e., conversion to T cell leukemia.

[0078] The present invention provides tetra-, penta-, and hexa-specific GNC (tetra-, penta-, and hexa-GNC) antibodies comprising a heavy chain (HC) and a light chain (LC) (Figure 1). Hexa-GNC antibodies can be configured to have five antigen-binding domains in the heavy chain (D1, D3, and D4) and light chain (D5 and D6), with a Fab region or dimeric receptor as the D2-binding domain, and possess a variety of structures selected from antibody fragments based on variable sequences (e.g., scFv), receptors encoded by non-variable sequences, and ligands. The VH and VL of the Fab region can be replaced with non-Fab dimers with or without binding specificities. In one embodiment, the Fc domains of the two chains are engineered to contain complementary mutations, also known as "knobs-into-holes," to promote heterodimer formation. Hexa-GNC antibodies contain six independent binding specificities for at least six antigens expressed by immune effector cells or target cancer cells. Compared to traditional combination therapies, the hexaGNC antibody class is designed to treat cancer as a single agent to improve efficacy and reduce manufacturing costs. In this way, the therapy simplifies clinical management SOPs, alleviates logistical concerns about multivariate administration, and becomes more affordable for patients.

[0079] The term "antibody" is used in the broadest sense and specifically covers single monoclonal antibodies (agonist and antagonist antibodies), antibody compositions with polyepitopic specificity, and antibody fragments (e.g., Fab, F(ab')2, and Fv), so long as they exhibit the desired biological activity. In some embodiments, antibodies may be monoclonal, polyclonal, chimeric, scFv, bispecific, biactive, human, and humanized antibodies. Examples of active fragments of known antigen-binding molecules include Fab, F(ab')2, scFv, and Fv fragments, as well as the products of Fab immunoglobulin expression libraries, and epitope-binding fragments of any of the aforementioned antibodies and fragments. In some embodiments, antibodies may include immunoglobulin molecules and immunoreactive portions of immunoglobulin molecules, i.e., molecules that contain a binding site that immunospecifically binds to an antigen. Immunoglobulins may be immunoglobulin molecules of any type (IgG, IgM, IgD, IgE, IgA, and IgY), class (IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass. In one embodiment, antibodies may be whole antibodies and any antigen-binding fragments derived from whole antibodies. A typical antibody generally refers to a heterotetrameric protein consisting of two heavy (H) chains and two light (L) chains. Each heavy chain contains a heavy chain variable domain (V H Each light chain consists of a light chain variable domain (V L V H Area and V L The region can be further divided into domains of hypervariable complementarity determining regions (CDRs) and more conserved regions called framework regions (FRs). H or V L ) is usually composed of three CDRs and four FRs arranged from the amino terminus to the carboxy terminus in the order FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions of the heavy and light chains contain binding regions that interact with antigens.

[0080] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies; i.e., the individual antibodies comprising the population are identical except for possible minor naturally occurring mutations. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, uncontaminated by other immunoglobulins. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the disclosure herein may be made by the hybridoma method first described by Kohler & Milstein, Nature, 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567).

[0081] Monoclonal antibodies may also include "chimeric" antibodies (immunoglobulins) in which portions of the heavy and / or light chains are identical to or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chains are identical to or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, and fragments of such antibodies, so long as the desired biological activity is exhibited (U.S. Pat. No. 4,816,567, and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855

[1984] ).

[0082] Monoclonal antibodies can be produced using a variety of methods, including mouse hybridoma or phage display (for a review, see Siegel. Transfus. Clin. Biol. 9:15-22 (2002)), or by molecular cloning of antibodies directly from primary B cells (see Tiller. New Biotechnol. 28:453-7 (2011)). In this disclosure, antibodies were generated by immunizing rabbits with both human PD-L1 protein and cells transiently expressing human PD-L1 on their cell surface. Rabbits are known to produce antibodies with high affinity, diversity, and specificity (Weber et al. Exp. Mol. Med. 49:e305). B cells from the immunized animals were cultured in vitro and screened for the production of anti-PD-L1 antibodies. In addition to rabbit immunization and subsequent B cell culture, other common strategies for antibody generation and discovery include immunization of other animals (e.g., mice) followed by display in hybridomas and / or phage, yeast, or mammalian cells; or display using synthetic variable gene libraries. Antibody variable genes are isolated using recombinant DNA technology, and the resulting antibodies are recombinantly expressed and further screened for desired characteristics, such as the ability to inhibit binding of PD-1 to PD-L1, the ability to bind to non-human primate PD-L1, or the ability to enhance human T cell activation. This general method of antibody discovery is similar to that described by Seeber et al., PLOS One. 9:e86184 (2014).

[0083] The term "antigen- or epitope-binding portion or fragment" refers to a fragment of an antibody capable of binding to an antigen. These fragments may retain the antigen-binding function of the intact antibody as well as additional functions. Examples of binding fragments include, but are not limited to, a single-chain Fv fragment (scFv), consisting of the VL and VH domains of a single arm of an antibody connected by a synthetic linker in a single polypeptide chain, or a Fab fragment, which is a monovalent fragment consisting of the VL, constant light (CL), VH, and constant heavy 1 (CH1) domains. Antibody fragments are produced using conventional methods known to those skilled in the art. Antibody fragments can be screened for utility using the same techniques used with intact antibodies.

[0084] "Antigen- or epitope-binding fragments" can be derived from the antibodies disclosed herein by many techniques known in the art. For example, purified monoclonal antibodies can be cleaved with an enzyme such as pepsin and subjected to HPLC gel filtration. Appropriate fractions containing Fab fragments can then be collected and concentrated by membrane filtration or the like. For further description of general techniques for isolating active fragments of antibodies, see, e.g., Khaw, BA et al. J. Nucl. Med. 23:1011-1019 (1982); Rousseaux et al. Methods Enzymology, 121:663-69, Academic Press, 1986.

[0085] Papain digestion of antibodies produces two identical antigen-binding fragments, called "Fab" fragments, each with a single antigen-binding site, and a residual "Fc" fragment, whose name reflects its ability to crystallize readily. Pepsin treatment produces an F(ab')2 fragment that has two antigen-binding sites and is capable of cross-linking antigen.

[0086] Fab fragments may contain the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab' fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab'-SH is the designation used herein for Fab' in which the cysteine ​​residues of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments with hinge cysteines between them. Other chemical linkages of antibody fragments are also known.

[0087] "Fv" is the minimum antibody fragment that contains a complete antigen-recognition and binding site. This region consists of a dimer of one heavy-chain variable domain and one light-chain variable domain in tight, non-covalent association. In this configuration, the three CDRs from each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody.

[0088] The "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda (λ), based on the amino acid sequences of their constant domains.

[0089] Depending on the amino acid sequence of the constant domain of the heavy chain, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and some of these can be further divided into subclasses (isotypes), e.g., IgG-1, IgG-2, IgG-3, IgG-4, IgA-1, and IgA-2. The heavy chain constant domains corresponding to the different classes of immunoglobulins are called α, delta, epsilon, γ, and μ, respectively. The subunit structures and three-dimensional configurations of the different classes of immunoglobulins are well known.

[0090] A "humanized antibody" refers to a type of engineered antibody that has CDRs derived from a non-human donor immunoglobulin, with the remaining immunoglobulin-derived portions of the molecule derived from one (or more) human immunoglobulins. Additionally, framework support residues may be altered to retain binding affinity. Methods for obtaining "humanized antibodies" are well known to those skilled in the art. (See, e.g., Queen et al., Proc. Natl Acad Sci USA, 86:10029-10032 (1989), Hodgson et al., Bio / Technology, 9:421 (1991)).

[0091] As used herein, the terms "polypeptide," "peptide," and "protein" are used interchangeably and are defined to mean a biomolecule composed of amino acids linked by peptide bonds.

[0092] As used herein, the terms "a," "an," and "the" are defined to mean "one or more," and include the plural unless the context requires otherwise.

[0093] "Isolated" refers to a biological molecule that is free from at least some of the components with which it naturally occurs. "Isolated," when used to describe various polypeptides disclosed herein, refers to a polypeptide that has been identified and separated and / or recovered from the cell or cell culture in which it is expressed. Typically, an isolated polypeptide is prepared by at least one purification step. "Isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigen-binding specificities.

[0094] By "recombinant" is meant that the antibody is produced in an exogenous host cell using recombinant nucleic acid techniques.

[0095] The term "antigen" refers to an entity or fragment thereof that is capable of eliciting an immune response in an organism, particularly an animal, more particularly a mammal, including a human. The term includes immunogens and regions thereof that are responsible for antigenicity or antigenic determinants.

[0096] Also, as used herein, the term "immunogenic" refers to a substance that induces or enhances the production of antibodies, T cells, or other reactive immune cells against the immunogenic agent and contributes to a human or animal immune response. An immune response occurs when an individual produces sufficient antibodies, T cells, and other reactive immune cells against the administered immunogenic composition disclosed herein to alleviate or ameliorate the disorder being treated.

[0097] "Specific binding" or "binds specifically" or "specific" for a particular antigen or epitope refers to binding that is distinct from non-specific interactions. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which is generally a molecule of similar structure that has no binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

[0098] The term "affinity" refers to the measure of the attractive force between two polypeptides, such as antibody / antigen or receptor / ligand. The inherent attractive force between two polypeptides can be expressed as the binding affinity equilibrium dissociation constant (KD) of a specific interaction. The KD binding affinity constant can be measured, for example, by biolayer interferometry. Here, KD is the ratio of kD (dissociation rate constant) to kD (association rate constant), i.e., KD = kD / kD.

[0099] Specific binding to a particular antigen or epitope is, for example, at least about 10 -4 M, at least about 10 -5 M, at least about 10 -6 M, at least about 10 -7 M, at least about 10 -8 M, at least about 10 -9 M, at least about 10 -10 M, at least about 10 -11 M, at least about 10 -12This can be demonstrated by an antibody having a KD for an antigen or epitope of M or greater, where KD refers to the equilibrium dissociation constant of a particular antibody-antigen interaction. Typically, an antibody that specifically binds to an antigen may have a KD for the antigen or epitope that is 20-, 50-, 100-, 500-, 1000-, 5000-, 10000-, or greater than that of a control molecule.

[0100] Specific binding to a particular antigen or epitope can also be demonstrated by an antibody having a K A or K A for the antigen or epitope that is at least 20-, 50-, 100-, 500-, 1000-, 5000-, 10000-, or greater than that for a control epitope, where K A or K A refers to the association rate of a particular antibody-antigen interaction.

[0101] The "homology" between two sequences is determined by the sequence identity. When the two sequences compared to each other are different in length, the sequence identity preferably relates to the percentage of nucleotide residues in the shorter sequence that are identical to the nucleotide residues in the longer sequence. Sequence identity can be conventionally determined using a computer program. Deviations that appear in the comparison of a given sequence with the above sequences disclosed herein may be caused by, for example, addition, deletion, substitution, insertion or recombination.

[0102] The disclosure herein may be more readily understood by reference to the following detailed description of specific embodiments and examples contained herein. Although the disclosure herein has been described with reference to specific details of specific embodiments thereof, such detailed description should not be construed as a limitation on the scope of the disclosure.

[0103] Example Example 1: Methods and Assays Expression and purification

[0104] DNA sequences encoding the heavy and light chains were cloned from custom gene fragments into the pTT5 vector using restriction cloning and / or Gibson assembly. Plasmid DNA was transiently transfected into ExpiCHO cells (Thermo A29133) according to the manufacturer's instructions to produce multispecific GNC proteins. Titers were measured after 7–9 days using a ForteBio Octet instrument equipped with a Protein A sensor.

[0105] GNC protein was purified by Protein A chromatography (Cytiva, 17549853), washed with phosphate-buffered saline (PBS), eluted with 50 mM sodium acetate (pH 3.6), and then immediately neutralized by adding 1 / 5 of a 1 M sodium acetate (pH 7.0). Protein quality was assessed after affinity purification by analytical size-exclusion chromatography (aSEC). aSEC was performed using an Acquity Arc Waters XBridge BEH SEC 300A, 7.8 x 300 mm, 3.5 μm column. The protein was further purified with a preparative SEC step using a Superdex 200 Increase 10 / 300 GL column. All subsequent assays were performed by aSEC with protein that was at least 90% of the target protein.

[0106] T cell-dependent cytotoxicity assay

[0107] T cell-dependent cytotoxicity (TDCC) assays were performed according to the method described by Nazarian et al. (2014). Target cells from established cancer cell lines (ADCC) were first transduced with a luciferase-expressing gene to generate luciferase-positive target cells. These target cells were then propagated in cell culture flasks. After expansion to appropriate numbers, they were lifted, counted, and reseeded into 384-well plates (Corning 3570) at the appropriate density depending on their previous growth characteristics using a BioTek EL406 liquid dispenser. For adherent cell lines, cells were allowed to adhere to the plates overnight in a CO2-controlled jacketed tissue culture incubator. Next, either PBMCs or previously expanded T cells (dynabeads) were plated at the appropriate effector / target ratio (typically 5:1), and the plates were treated with serial dilutions of the test T cell targeting agent. Test substance experiments were performed in quadruplicate, and 96-well dilution blocks were stamped into 384-well quadrants using a robot (Opentrons OT-2 liquid handling robot). TDCC assay plates were incubated for 72–96 h. Cell viability curves were read using the Promega Bright-glo luciferase assay kit. Briefly, 20 μL was added to the TDCC assay plate, and after approximately 15 min of incubation, luminescence was measured using a BMG Clariostar plate reader. Killing curves and EC50 values ​​were analyzed and plotted using GraphPad software.

[0108] SEC-MALS Analytical size-exclusion chromatography (SEC) was performed in combination with multi-angle light scattering (MALS), absorbance (UV), and / or refractive index (RI) concentration detectors. SEC-MALS is typically used in the analytical characterization of antibodies and in early-phase clinical trials to support FDA IND submissions. Size exclusion was performed using an Acquity Arc Waters and XBridge BEH SEC300A, 7.8 x 300 mm, 3.5 μm column. The MALS component uses a Wyatt miniDAWN TREOS / OPtilab T-rEX system. Molecular weight can be determined from measurements of the change in solution refractive index, Δn, with a change in molecular concentration, Δc (measured as dn / dc (=Δn / Δc) using an Optilab T-rEX differential refractometer). The intensity of light scattered by a molecule, as measured by the miniDAWN TREOS multi-angle light scattering (MALS) detector, is directly proportional to its molar mass.

[0109] OCTET The ForteBio Octet platform applies biolayer interferometry (BLI) as a label-free technique for measuring protein-protein interactions. This is an optical analysis technique that analyzes the interference pattern of white light reflected from two surfaces: an immobilized protein layer and an internal reference layer on a biosensor chip. Changes in the number of molecules bound to the biosensor tip result in a change in the interference pattern, which can be measured in real time. In this method, binding of an antibody immobilized on the tip surface of an anti-human IgG Fc capture (AHC) biosensor to an antigen in solution increases the optical thickness of the biosensor tip, resulting in a wavelength shift Δλ that directly reflects changes in the thickness of the biological layer. The interaction of these two molecules is measured in real time, allowing precise and accurate monitoring of binding specificity, association and dissociation rates, or concentration. Unbound molecules, changes in the refractive index of the surrounding medium, or changes in flow rate do not affect the interference pattern. In the Octet system, the GNC protein is immobilized using an AHC chip, and the binding of the GNC protein to the target antigen can be easily analyzed using purified antigen as the analyte at a single concentration (e.g., 100 nM) or at a series of concentrations (e.g., seven 1:2 serial dilutions starting from 200 nM).

[0110] Tm by dynamic light scattering (DLS) The hydrodynamic radius (Rh) of antibody samples (1 mg / ml) was measured using a DynaPro plate reader from 25°C to 75°C in 1°C increments at a rate of 0.26°C / min. A total of three 5-second acquisitions were collected at each temperature. The radius, onset temperature, and midpoint of the transition curve (Tm) at which Rh began to change significantly were calculated using DYNAMICS 7.8.1.3 software (Wyatt Technologies).

[0111] Quantitative flow cytometry (qFACS) CountBright absolute counting beads (Thermo C36950) were used for calibration, and the primary antibodies panitumumab (EGFR), anti-HER3 from MM111 (HER3), PL221G5 (PD-L1), TF 3H8-1 (CEA), and trastuzumab (HER2) were used to quantify the corresponding receptor numbers in various tumor cell lines (Wang L et al. Curr Protoc. Cytom. 2016).

[0112] Example 2: GNC antibody having NKG2D as one of the binding domains NKG2D is a major recognition receptor for the detection and elimination of transformed and infected cells, and its ligands are induced during cellular stress as a result of genomic stress, such as infection or cancer. In humans, NKG2D is encoded by the KLRK1 gene, which is located in the NK gene complex (NKC), and is involved in the expression of NK cells, γδ T cells, and CD8 + It is expressed by αβ T cells. The human NKG2D receptor complex assembles into a hexameric structure, while NKG2D itself forms a homodimer, and its ectodomain is responsible for ligand binding. On NK cells, NKG2D functions as an activating receptor and can itself induce cytotoxicity. CD8 + The function of NKG2D on T cells is to deliver costimulatory signals to activate them. The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) encodes essentially all human natural killer (NK), γδT, and CD8 T cells. + It encodes a membrane-bound protein that acts as a stimulatory ligand for the activating receptor NKG2D, which is expressed on the surface of αβ T cells. While the MICA protein is absent from most cells, it can be induced by infection or oncogenic transformation and is frequently expressed in epithelial tumors. Upon binding to MICA, NKG2D activates the cytolytic response of NK cells and γδ T cells against MICA-expressing infected and tumor cells. Thus, membrane-bound MICA serves as a signal for the early immune response against infection and naturally occurring tumors. On the other hand, human tumor cells spontaneously release a soluble form of MICA, which causes downregulation of NKG2D and promotes the activation of NK and CD8 T cells.+ This causes a serious impairment of T cell anti-tumor immune responses. This is thought to promote tumor immune evasion and weaken host resistance to infections that may be neutralized by free NKG2D. In this context, and by definition of the GNC protein, NKG2D is one of the cytotoxic cell-binding moieties (see applicant's application PCT / US2018 / 039160; the entire contents of which are incorporated herein).

[0113] GNC antibodies with NKG2D ligand-binding specificity contain a common core antibody domain, and their Fc regions may or may not have effector function. Tetra-GNC antibodies were generated with an NKG2D dimer as one of the binding domains on the heavy chain (HC) (Table 1). These antibodies contained two additional scFv domains (containing binding domains for 4-1BB, a TNF superfamily receptor typically expressed on activated T cells (SI-49E1, SI-49E2, SI-49E3, and SI-49E4; Table 1)) or one additional scFv and 41BBL (trimeric form) (typically found on antigen-presenting cells (APCs) and binding to 4-1BB (SI-49E11, SI-49E12, and SI-49E13; Table 1)). These four binding domains (D1 to D4) were fused via a G / S linker region and expressed as a single heavy chain (HC, chain A, or chain 1). According to the definition shown in Figure 1, these types of tetra-GNC antibodies are characterized by having one scFv (D1) located at the N-terminus of the VH domain (D2 or Fab) and two scFvs (D3 and D4) consecutively linked to the Fc region, whereas the light chain (LC) contains only the VL domain (D2 or Fab) in its native configuration. One strategy for producing penta-GNC antibodies with NKG2D-binding specificity is to engineer an additional NKG2D tandem repeat homodimer at the N- (D6) or C- (D5) terminus of the LC (Figure 1). Five D5-pentaGNC antibodies were generated that contain an NKG2D dimer as the binding domain from the LC (SI-49P1, SI-49P2, SI-49P3, SI-49P4, and SI-49P5; Table 2). These D5-pentaGNC antibodies feature a single cancer-targeting moiety (D2) combined with four cytotoxic binding moieties: anti-CD3, anti-PD-L1, anti-4-1BB, and NKG2D. Table 3 provides information on both exemplary cancer-targeting moieties and cytotoxic binding moieties as independent binding domains. According to this definition, PD-L1 is expressed on cancer cells as an immune checkpoint marker, but is not classified as a cancer-targeting moiety.These D5-pentaGNC antibodies are composed of a core antibody-binding domain with three additional scFv-binding regions in the HC and one NKG2D tandem repeat homodimer in the LC (for a total of five different specificities), although the configuration can vary. For example, the pentaGNC antibody may contain two additional scFv-binding regions, one TNF superfamily (trimeric) domain, and one NKG2D tandem repeat homodimer (for a total of five different specificities). Because NKG2D and 41BBL do not have typical antigen-binding domain structures, i.e., Fab and scFv, GNC antibodies with Fab in the core are sometimes referred to interchangeably as GNC molecules or GNC proteins elsewhere. Furthermore, the domain structure may be engineered to stabilize these multispecific GNC proteins. For example, each scFv domain may have both disulfide-stapled and non-stapled variants at vL100 and vH44, selected to stabilize the overall structure.

[0114] Analytical SEC analysis demonstrated the stability and high quality of purified tetra-GNC antibodies containing the NKG2D receptor and 41BBL, as well as multiple D5-penta-GNC antibodies with NKG2D binding specificity from LC (including SI-49E1, SI-49E2, SI-49E3, SI-49E4, SI-49E11, SI-49E12, SI-49E13, SI-49P1, SI-49P2, SI-49P3, and SI-49P4) (Figures 2A-2C). This demonstrates that these atypical GNC antibodies can be easily purified and maintained in a stable state.

[0115] Example 3: Comparison of the potency of GNC antibodies with NKG2D as one of the binding domains On NK cells, NKG2D functions as an activating receptor and can itself cause cytotoxicity, while CD8 +In T cells, the function of NKG2D is to deliver costimulatory signals to activate them. NKG2D forms homodimers, and its ectodomain serves for ligand binding. This function allows NKG2D to serve as a non-variable sequence-based binding domain in the GNC format, and other binding domains can be added to create a class of multispecific NKG2D-GNC proteins. In one GNC format, individual NKG2D monomers are incorporated into the D2 position of the heavy and light chains, forming a dimeric NKG2D receptor through HC / LC dimerization. Thus, NKG2D can function as a receptor for the multispecific antibody-like protein GNC molecule to bind its ligand. In other GNC formats, NKG2D tandem repeats are engineered by adding a (GxSy)n linker between individual NKG2D monomers that homodimerize to form a functional dimeric receptor. This NKG2D tandem dimer structure can be located at D1, D3, D4, D5, or D6.

[0116] To evaluate the influence of the NKG2D position on the tetra-GNC antibodies, SI-49E1, SI-49E2, SI-49E3, and SI-49E4 were used in TDCC assays (Figure 3). Using the MICA-expressing MDA-MB-231 cell line, all four NKG2D tetra-GNC antibodies demonstrated higher potency than the control antibodies SI-49X1 (bispecific NKG2D-αCD3-Fc antibody) and SI-49X2 (bispecific Fc-αCD3-NKG2D antibody). Both control antibodies SI-49X1 and SI-49X2 lack anti-PD-L1 and anti-4-1BB scFv. This result suggests that binding specificity for PD-L1 and / or 4-1BB contributes to toxicity. The minor differences among the four NKG2D tetra-GNC antibodies may largely reflect differences in their composition and accessibility to immune cells.

[0117] The effect of NKG2D positioning on the penta-GNC antibodies was assessed by TDCC assay using SI-49P1, SI-49P2, SI-49P3, SI-49P4, and SI-49P5 (Table 2) (Figure 4). The NKG2D-αMSLN penta-GNC antibody SI-49P1 killed cells more potently than the tetra-GNC control antibodies SI-51E4 and SI-51E1 and the NKG2D-α mesothelin (αMSLN) control antibody SI-51X1. This observation indicates a trend toward improved potency due to the addition and positioning of NKG2D to the tetra-GNC antibody. The control antibody SI-51X1, a trispecific αNKG2D-LC / αCD3-αMSLN-Fc lacking αPD-L1 and α4-1BB, exhibited lower potency, indicating that both the αPD-L1 and α4-1BB domains can enhance toxicity. Cell killing efficacy is Penta GNC > Tetra GNC > Penta GNC control antibody.

[0118] To quantify the ability of NKG2D receptor domain dimers to redirect T cells to kill MICA-bearing tumor cells in the context of tetra-GNC or penta-GNC antibodies, we performed a TDCC assay using MDA-MB-231 target cells. Test articles included a control tetra-GNC antibody with a negative control anti-FITC domain at D2 (SI-38E72, αCD3xαFITCxαPD-L1xα4-1BB), tetra-GNC antibodies with binding domains at different GNC positions (SI-49E1, SI-49E2, SI-49E3, SI-49E4, NKG2DxαCD3xαPD-L1xα4-1BB), and penta-GNC with an additional αMSLN-binding domain (SI-49P1, αCD3xαMSLNxαPD-L1xα4-1BBxNKG2D). The effector cell:target cell ratio (E:T) was 5:1. Purified T cells, target cells, and drug dilutions were incubated for 96 hours, after which luminescence readings representing remaining tumor cells were taken. Note that some experiments were performed on different days, so the absolute EC50 values ​​may vary. Nevertheless, the results in Table 4 show that all Tetra-GNC antibodies containing the NKG2D domain have significantly higher TDCC potencies than their counterparts (SI-38E72) that do not contain NKG2D, ranging from approximately 10-fold (SI-49E2) to over 130-fold (SI-49E4). While the differences among these Tetra-GNC antibodies may be due to the composition of the four binding domains within the same group, the addition of an anti-TAA moiety significantly increased the potency of the penta-GNC antibody SI-49P1 by over 600-fold. Therefore, the addition of a cytotoxic binding moiety such as NKG2D can improve potency, and the addition of an anti-TAA binding moiety can specifically increase the efficacy of T cell-mediated tumor cell killing.

[0119] Example 4: Mutations that remove light chain contaminants Antibody-based proteins are most often purified by Protein A affinity chromatography. In this case, Protein A resin binds to the C of the Fc domain. H2 -C H3 Protein A captures antibodies at the binding sites at the interface.H3 Family Fv V H Most antibody-based platforms also bind to the V H This is not a problem as the domains are generally on the heavy chain. H3 When an scFv containing V binds to a light chain, it is converted to V during purification. H domains bind to the Protein A resin, and light chain monomers and dimers may contaminate the desired heavy-light chain heterotetramer. H3 A potential obstacle in generating multispecific antibodies containing domains is the presence of additional contaminants in the Protein A elution. This is particularly problematic when light chains are expressed more efficiently than heavy chains, resulting in large amounts of light chain contaminants co-purifying with the protein assembly of interest.

[0120] To rationally disrupt protein A binding of VH3 family members, we employed a structural approach to disrupt the binding interface. The crystal structure 1DEE (Graille M. et al., Proc. Nat. Acad. Sci. 2000) showed that residue R19 (Kabat numbering) of VH3 makes direct contact with two side chains of protein A domain D. In particular, eliminating contact with Q32 and D36 significantly weakens the interaction. Therefore, R19 was mutated to serine, which does not form these interactions due to its short side chain. Furthermore, S19 is naturally present in other VH family members, suggesting that it may be less immunogenic than other substitutions.

[0121] V on the GNC light chain H3The mutation R19S (Kabat numbering) was incorporated into the FR1 region of the VH domain of the scFv containing the antibody. Specifically, the hexaGNC antibody SI-55-H11 contained an R19S mutation in the light chain sequence encoding the anti-HER3 scFv domain in D5 and the anti-CD19 scFv in domain 6. Because the target residue is located in the Protein A binding interface, the R to S mutation disrupts the interaction with Protein A. Elimination of Protein A binding in the light chain scFv prevents binding of light chain monomers and dimers to Protein A during purification. This results in a more homogeneous product free of light chain contaminants. Up to two V per light chain can be used. H3 In the case of hexaGNC, which can contain scFv, this mutation is particularly important for efficient purification of the desired product.

[0122] Example 5: Comparison of the potency of multispecific GNC antibodies with different binding domain structures

[0123] In the general scheme of the multispecific GNC protein (Figure 1), each binding domain of the multispecific GNC antibody can be a Fab or scFv based on the variable sequence, or a ligand, receptor, or other binding structure based on the non-variable sequence. To evaluate how the structural diversity of each binding domain affects the overall function of the multispecific GNC antibody, a TDCC assay was performed to induce T cell-mediated killing of pancreatic cancer cells (BxPC3). As shown in Table 5, three penta-GNC antibodies (SI-1P1, SI-55P9, and SI-55P10) and one hexa-GNC antibody (SI-55H11) were used to evaluate changes in binding specificity for EGFR, HER3, CD19, CD3, and 4-1BB. All test substances contained the αPD-L1 scFv at position D3, with no changes in its position or structure. For binding specificity to EGFR, changes involved position D1 vs. D2. For binding, changes included both structure (stapled vs. unstapled) and position (D1 vs. D2). For binding specificity to 4-1BB, changes included both structure and binding mechanism (41BBL-mediated variable sequence-based scFv and non-variable sequence-based ligand-receptor interaction, i.e., interaction of the 4-1BB ligand trimer to the 4-1BB receptor). For binding specificity to CD19, changes were related to the humanized variable sequence. For binding specificity to HER3, since HER3 was not detected on the surface of BXPC3 cells, this difference accounted for this group as either the tetra-GNC, penta-GNC, or hexa-GNC antibodies (see Table 9).

[0124] The TDCC assay was set up under the same conditions (e.g., effector:target cell ratio (E:T) 5:1). Purified T cells, target cells, and drug dilutions were incubated for 72 hours, after which luminescence, representing the remaining tumor cells, was read. Note that because some experiments were performed on different days, EC50 values ​​may vary between experiments within the margin of error. Nevertheless, the potency of these penta-GNC and hexa-GNC antibodies was less than 1 pM, within a 10-fold range, indicating that structural changes may significantly improve manufacturing cost and feasibility over their effectiveness in killing BXPC3 cells. In this context, the composition of binding specificities remains a determining factor for creating multispecific GNC antibodies targeting specific forms of cancer.

[0125] Example 6: Composition of Part 1 and Part 2 of Multispecific GNC Antibody Multispecific GNC antibodies with up to six binding specificities can be applied to antibody therapies with the highest cancer cell killing potential. For example, EC50 values ​​can be reduced from nM to pM or even fM levels. Successful and highly effective multispecific GNC antibodies depend on the composition of both the part 1 and part 2 antigens. Table 4 shows the comparative potency of the four part 1 binding specificities (i.e., αCD3, αPD-L1, α4-1BB, and NKG2D) in the tetra-GNC antibody by TDCC assay using MDA-MB-231 cells as target breast cancer cells. Compared to a control antibody (SI-38E72) containing three part 1 binding domains (i.e., αCD3, αPD-L1, and α4-1BB as D1, D3, and D4 of the HC, respectively), the addition of a fourth part 1 binding domain to the NKG2D dimeric receptor based on the non-variable sequence improved potency by approximately 10- to 130-fold, depending on the configuration. However, the addition of the anti-TAA moiety significantly increased the potency of the penta-GNC antibody (SI-55H11) by up to 600-fold.

[0126] To evaluate the binding specificity of part 1 in combination with the three part 1-binding domains, a TDCC assay was performed using the breast cancer cell line MDA-MB-231 as the target cell. All test articles contained αCD3, αPD-L1, and α-4-1BBscFv at positions D1, D3, and D4, respectively. Tetra-GNC antibody (SI-38E72) (which lacks the part 1-binding domain and has an α-FITC domain at D2 that is not specific for any tumor antigen) was used as a control. The other Tetra GNC test substances had various binding domains in D2 (SI-55E: αEGFR cetuximab; SI-55E2: αEGFR panitumumab; SI-50E1: αHER2 trastuzumab; and SI-51E1: αmesothelin amatuximab). The Penta GNC antibody (SI-1P1) had αEGFR cetuximab in D2 and αHER3 MM111scFv in D5. The effector:target cell ratio (E:T) was 5:1 or 10:1. Purified T cells, target cells, and drug dilutions were incubated for 96 hours, after which luminescence readings representing remaining tumor cells were taken. Note that because some experiments were performed on different days, EC50 values ​​may vary but are within the margin of error. Nevertheless, the results show that all GNC antibodies containing the αTAA domain in D2 induced significantly (20- to 100-fold) more potent TDCC than the control containing αFITC in D2 (Table 6). The EC50 of the penta-GNC antibody (SI-1P1) was similar to that of tetra-GNC, indicating that adding domains can improve TAA selectivity while retaining potent TDCC.

[0127] Example 7: Screening of TAAs using tetra-GNC constructs with three moiety 1 linkages The configuration of three portion 1 binding domains fixed at D1, D3, and D4 (Table 6) can be used as a backbone HC to accurately identify novel and / or effective portion 2 binding domains of TAA. To evaluate the ability of multispecific GNC antibodies targeting different tumor antigens to induce T cell-mediated killing, a TDCC assay was performed using the cervical cancer cell line HeLa as the target cell. All test substances possessed αCD3, αPD-L1, and α4-1BBscFv at D1, D3, and D4, respectively. The tetraGNC antibody (SI-38E72) was used as a control because it possessed an αFITC domain at D2 that is not specific to any tumor antigen. Other tetraGNC test substances possessed various binding domains at D2 (Table 7). The effector cell:target cell ratio (E:T) was 10:1. Purified T cells, target cells, and drug dilutions were incubated for 96 hours, after which luminescence, representing the remaining tumor cells, was read. Note that some experiments were performed on different days, so the EC50 values ​​may vary, but are within the margin of error. Nevertheless, results from experiments performed on the same day show that two anti-EGFR tetra-GNC antibodies (SI-55E1 (Cet) and SI-55E2 (Pan)) killed more than 50% of cancer cells with potencies of 13 pM and 9 pM, respectively (Figure 5). The other test substances (SI-51E1, SI-52E1, SI-50E2, SI-54E1, SI-55E3, SI-56E1, SI-57E1, and SI-38E17) killed less than 20% of the inoculated cells, demonstrating weaker killing activity. Therefore, their EC50 values ​​were not as strong as those of SI-55E1 and SI-55E2. SI-55E3 has an anti-EGFR binding domain in the Fab derived from D2 or nimotuzumab, and its binding affinity to EGFR is lower than that of SI-55E1 (panitumumab) and SI-55E2 (cetuximab) (Applicant's application PCT / US2020 / 059230; the entire contents of which are incorporated herein). Surprisingly, SI-55E3 was one of the antibodies that showed weak killing ability. This finding indicates that both binding specificity and affinity play a role in multispecific GNC antibody-mediated TDCC.

[0128] Example 8: Comparison of the efficacy of the same multispecific GNC antibody to kill different cancer cells

[0129] To further characterize the comparative potency of SI-55E1 and SI-55E2, which have the same portion 1 binding domain and target EGFR, the MDA-MB-231 cell line was used in a TDCC assay. Two additional antibodies targeting both EGFR and HER3 were used in the same experiment. SI-1P2 is a penta-GNC antibody with an additional portion 2 domain that binds to HER3 in addition to the portion 1 binding domain of the same structure as SI-55E1 and SI-55E2. SI-1 is a bispecific antibody targeting both EGFR and HER3 in the absence of the portion 1 binding domain. The materials and methods for this TDCC assay were the same as those described in Example 1. As shown in Figure 6, SI-55E1, SI-55E2, and SI-1P2 exerted comparable potencies, as indicated by overlapping dose-survival curves, with EC50 values ​​ranging from 17 to 29 fM (Table 6). In contrast, SI-1 showed no response at sub-nM doses in the same experiment. This result supported the notion that the three portion 1 binding domains (CD3, PD-L1, and 4-1BB) contribute significantly to the efficacy of multispecific GNC antibodies.

[0130] To measure the additional effect of a portion 1 binding domain, such as anti-CD3, two tetraGNC antibodies (SI-50E1 and SI-50E6) and one biGNC antibody (SI-50X1) were analyzed by TDCC assay using the MDA-MB-231 cell line as the target cell. All three antibodies have the same binding specificity for trastuzumab-derived HER2 (Table 6). SI-50E1 and SI-50E6 have the same configuration of portion 1 and portion 2 binding domains, but the scFv domain of SI-50E6 was engineered with an additional disulfide bond (i.e., stapled) to enhance stability, whereas the scFv domain of SI-50E1 was not stapled. SI-50X1 is a bispecific antibody targeting both CD3 and HER2. TDCC dose-response curves clearly demonstrate that all three GNC antibodies are potent, with EC50 values ​​in the fM range (Figure 7). The differences in the curves and EC values ​​were due to the absence or presence of the portion 2 binding domains for PD-L1 and 4-1BB among the three antibodies.

[0131] Example 9: Selection of TAA for multispecific GNC antibodies and assembly of part 2 binding domains

[0132] Antibody therapies employ various strategies to directly or indirectly kill cancer cells, both of which rely on binding to surface antigens. However, cancer cells can evolve to acquire the ability to evade antibody and / or immune cell recognition. Multispecific GNC antibodies capable of binding up to six specificities demonstrated the greatest potency, as measured by in vitro EC50s in the pM and fM ranges. Highly effective multispecific GNC antibodies depend on the composition of both the part 1 and part 2 antigens. Here, the three part 1 binding domains (CD3, PD-L1, and 4-1BB) in the construct (D1, D3, and D4 of the HC, respectively) provide the backbone of the multispecific GNC antibody. This formatted GNC antibody enables the selection, screening, and optimization of TAA targeting cancer cells (Figure 8).

[0133] To demonstrate the importance of TAAs surface expression profiles, quantitative flow cytometry (qFACS) was performed to quantify the approximate number of receptors per cell for various tumor targets. EGFR, HER2, and HER3 are EGFR family members whose expression is typically upregulated by solid tumors, and PD-L1 is a target for inhibiting immune checkpoint signaling utilized in a subset of human cancers. Nevertheless, surface expression of HER3 and PD-L1 was undetectable on MDA-MB-232 and HeLa cells, respectively (Table 8). This observation may explain the lack of synthetic lethal effect when targeting both EGFR and HER3 with SI-1P1 compared with SI-55E1, SI-55E2, and SI-50E1, which target EGFR or HER2, respectively (Table 6). It may also be interpreted that the failure of a control antibody (SI-38E72) to induce TDCC is likely due to the absence of PD-L1 in HeLa cells (Table 7). In light of the evolution and dynamic expression profiles of cancer cells, any candidate antibody can be tested for TDCC using the various types of cancer cells shown in Table 9.

[0134] To screen for TAAs, a modular cloning platform can be used to efficiently identify TAA or TAA epitopes for assembling the two binding domains of multispecific GNC antibodies. For example, TAA-Fc tetraGNC-1 and TAA-Fc tetraGNC-2 are two groups of tetraGNC antibodies with the same pairwise binding specificity. The only difference is that all TAA-Fc tetraGNC-2 antibodies contain stapled scFv domains D1, D3, and D4 (VH44→C and VL100→C mutations) in the HC. In this case, the HC was exchanged to generate two groups of tetraGNC antibodies. In other examples, the LC can be exchanged to generate multispecific GNC antibodies with additional TAA binding domains (e.g., SI-55P10 to SI-55H11 and SI-55E1 to SI-1P1). This modular cloning platform allows efficient assembly of multispecific GNC antibodies containing up to three TAAs starting from a single anti-TAA monoclonal antibody.

[0135] Example 10: Function of multispecific GNC proteins with receptors at the D2 position

[0136] To further validate the flexibility of the GNC platform to accommodate diverse binding domains at each molecular position, we produced a group of proteins bearing the NKG2D receptor at the D2 position (Table 10). When monomeric NKG2D was incorporated into the D2 position of both GNC chains, the NKG2D monomers were predicted to dimerize upon interchain association. SI-49R21 is a monospecific GNC (antibody-like protein) bearing the NKG2D receptor instead of the antibody VH / VL domains. SI-49R22 has the same format, except that its Fc domain also contains knobs-into-holes mutations for heterodimerization (Chain A: T366S / L368A / Y407V; and Chain B: T366W). SI-49R23 is a monospecific protein with NKG2D fused directly to the antibody Fc domain, and SI-49R24 has the same structure but additionally contains knobs-into-holes mutations in the Fc domain. SI-49R19 is a bispecific GNC with an anti-CD3 scFv at D1 and an NKG2D at D2, and SI-49R18 is a trispecific GNC with an anti-CD19 at D6. SI-49E15 has an anti-CD3 scFv at D1, an NKG2D at D2, an anti-PD-L1 scFv at D3, and an anti-4-1BB scFv at D4. SI-49P6 has the same domains as SI-49E15 but also has an anti-CD19 scFv at D6. SI-49P7 has the same structure as SI-49P6, except that it contains a 4-1BB ligand trimer at D4 instead of the anti-4-1BB scFv.

[0137] All proteins with NKG2D at D2 were successfully expressed and purified. Octet binding was performed to verify the functionality of the NKG2D receptor at the D2 position. GNC proteins were loaded onto an AHC sensor at 5 μg / ml and then bound to a 1:2 serial dilution (highest concentration 100 nM) of human MICA (Acro, MIA-H5221). The binding affinities (KD values) obtained from a global fit to a 1:1 binding model are shown in Table 11. Mono-, bi-, tri-, tetra-, and penta-GNC proteins with NKG2D at D2 were shown to retain strong binding to the NKG2D ligand MICA, as evidenced by KD values ​​of less than 20 nM.

[0138] Example 11: Antigen binding independent of GNC position, humanization, or domain format

[0139] To further demonstrate the adaptability of the GNC platform, we produced a group of hexaspecific GNC proteins targeting the same antigen (CD3xEGFRxPD-L1x4-1BBxCD19xHER3). This group contained an anti-PD-L1 scFv at D3, an anti-4-1BB scFv at D4, an anti-HER3 scFv at D5, and an anti-CD19 scFv at D6. Two molecules (SI-77H4 and SI-77H5) contained an anti-CD3 scFv at D1 and an anti-EGFR Fab at D2; the difference was that the anti-EGFR domain of SI-77H4 was humanized, while the anti-EGFR domain of SI-77H5 retained the murine sequence. Two molecules (SI-55H11 and SI-55H12) contain an anti-EGFR scFv in D1 and an anti-CD3 Fab in D2, with the difference being that the D2 VH / VL contains a disulfide staple in SI-55H11 (VH-44C, VL-100C) but not in SI-55H12. Thus, this group was able to determine whether the D1 / D2 configuration affects either protein expression characteristics or binding affinity to the target tumor-associated antigen.

[0140] The proteins were transiently expressed in ExpiCHO cells as described in Example 1. After approximately 8 days, the GNC titer was measured using a Protein A sensor on the Octet platform (Table 12). The results demonstrate that the hexaspecific GNC proteins were well expressed (≥30 μg / ml) regardless of the position and format of the anti-EGFR and anti-CD3 domains. After the initial Protein A purification step, all proteins had similarly low levels of aggregation, with target protein percentages ranging from 72 to 85% (Table 12). Next, the affinity of the anti-EGFR domain for human EGFR was evaluated by loading the GNC protein onto an AHC sensor and using a single concentration (100 nM) of His-tagged human EGFR (expressed in-house) as the analyte. As shown in Table 12, the position and format of the anti-EGFR and anti-CD3 domains did not significantly affect EGFR binding affinity (KD values ​​within approximately 2-fold). Therefore, the GNC protein retains full functionality regardless of the position of the anti-TAA and anti-CD3 domains between D1 and D2.

[0141] [Table 1] JPEG2025069123000002.jpg16125

[0142] [Table 2]

[0143] [Table 3]

[0144] [Table 4]

[0145] [Table 5] a 284A10: See applicant's application PCT / US2018 / 039143 b SI-huBU12: See applicant's application PCT / US2020 / 059230

[0146] [Table 6]

[0147] [Table 7]

[0148] [Table 8]

[0149] [Table 9]

[0150] [Table 10] *SI-49R22 contains a heterodimerized Fc with knobs-into-holes mutations (chain A: T366S / L368A / Y407V; chain B: T366W). **SI-49R23 lacks the CH1 / CL domain. ***SI-49R24 contains a heterodimerized Fc with knobs-into-holes mutations (chain A: T366S / L368A / Y407V; chain B: T366W) and lacks the CH1 / CL domains.

[0151] [Table 11]

[0152] [Table 12] *SI-55H11 D2 contains a disulfide staple between VH and VL (VH-44C, VL-100C).

[0153] JPEG2025069123000014.jpg221160 JPEG2025069123000015.jpg136160 JPEG2025069123000016.jpg157126 CDR's underlined in amino acid sequences Chain A: HC or Chain 1 Chain B: LC or Chain 2 >SEQ ID 1 SI-49E1 chain A nt >SEQ ID 2 SI-49E1 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 3 SI-49E1 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 4 SI-49E1 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 5 SI-49E2 chain A nt >SEQ ID 6 SI-49E2 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKGGGGSGGGGSGEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIK >SEQ ID 7 SI-49E2 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT > SEQ ID 8 SI-49E2 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 9 SI-49E3 chain A nt >SEQ ID 10 SI-49E3 chain A aa DVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSTGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 11 SI-49E3 chain B nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 12 SI-49E3 chain B aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 13 SI-49E4 chain A nt >SEQ ID 14 SI-49E4 chain A aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSTGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 15 SI-49E4 chain B nt GACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 16 SI-49E4 chain B aa DVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 17 SI-49E11 chain A nt >SEQ ID 18 SI-49E11 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 19 SI-49E11 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 20 SI-49E11 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 21 SI-49E12 chain A nt >SEQ ID 22 SI-49E12 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVVDGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSA FGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSKPGSGEGSTGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGSGEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIK >SEQ ID 23 SI-49E12 chain B nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 24 SI-49E12 chain B aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 25 SI-49E13 chain A nt >SEQ ID 26 SI-49E13 chain A aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLSTGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 27 SI-49E13 chain B nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 28 SI-49E13 chain B aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 29 SI-49E14 chain A nt >SEQ ID 30 SI-49E14 chain A aa DIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSTGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNIWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 31 SI-49E14 chain B nt >SEQ ID 32 SI-49E14 chain B aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 33 SI-1P1 chain A nt >SEQ ID 34 SI-1P1 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 35 SI-1P1 chain B nt >SEQ ID 36 SI-1P1 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 37 SI-1P2 chain A nt >SEQ ID 38 SI-1P2 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 39 SI-1P2 chain B nt >SEQ ID 40 SI-1P2 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKCLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 41 SI-1P4 chain A nt >SEQ ID 42 SI-1P4 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 43 SI-1P4 chain B nt >SEQ ID 44 SI-1P4 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGCGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKCLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 45 SI-39P1 chain A nt >SEQ ID 46 SI-39P1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSGGGGSGGGGSDVQLQESGPSLVKPSQSLSLTCTVTGYSIT SDFAWN WIRQFPGNKLEWMG YISYSGNTRYNPSLKS RISITRDTSKNQFFLQLNSVTIEDTATYYCVT AGRGFPY WGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSQSLVESGGGLVQPGGSLRLSCAASGFSFS SNYWIC WVRQAPGKGLEWIA CIYVGSSGDTYYASSAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DSSSYYMFNL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSALVMTQSPSTLSASVGDRVTINC QASEDIDTYLA WYQQKPGKAPKLLIF YASDLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGGYYTSSADTRGA FGGGTKVEIK >SEQ ID 47 SI-39P1 chain B nt >SEQ ID 48 SI-39P1 chain B aa DILMTQSPSSMSVSLGDTVSITC HSSQDINSNIG WLQQRPGKSFKGLIY HGTNLDD EVPSRFSGSGSGADYSLTISSLESEDFADYYC VQYAQFPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYC SSYGSSSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSS >SEQ ID 49 SI-38P5 chain A nt >SEQ ID 50 SI-38P5 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 51 SI-38P5 chain B nt >SEQ ID 52 SI-38P5 chain B aa QIVLSQSPAILSASPGEKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYC QQWTSNPPT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFS SSWIG WVRQAPGKGLEWMG IIYPDDSDTRYSPSFQG QVTISADKSIRTAYLQWSSLKASDTAMYYCAR HVTMIWGVIIDF WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAIQLTQSPSSLSASVGDRVTITC RASQGISSALA WYQQKPGKAPKLLIY DASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFNSYPFT FGPGTKVDIK >SEQ ID 53 SI-38P6 chain A nt >SEQ ID 54 SI-38P6 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 55 SI-38P6 chain B nt >SEQ ID 56 SI-38P6 chain B aa QIVLSQSPAILSASPGEKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYC QQWTSNPPT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFS SSWIG WVRQAPGKCLEWMG IIYPDDSDTRYSPSFQG QVTISADKSIRTAYLQWSSLKASDTAMYYCAR HVTMIWGVIIDF WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSAIQLTQSPSSLSASVGDRVTITC QUESTIONS WYQQKPGKAPKLLIY DASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFNSYPFT FGCGTKVDIK >SEQ ID 57 SI-49P1 chain A nt >SEQ ID 58 SI-49P1 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSQVQLQQSGPELEKPGASVKISCKASGYSFT GYTMN WVKQSHGKSLEWIG COLOR SYNQKFRG KATLTVDKSSSTAYMDLLSLTSEDSAVYFCAR GGYDGRGFDY WGSGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 59 SI-49P1 chain B nt >SEQ ID 60 SI-49P1 chain B aa DIELTQSPAIMSASPGEKVTMTC SASSSVSYMH WYQQKSGTSPKRWIY DTSKLAS GVPGRFSGSGSGNSYSLTISSVEAEDDATYYC QQWSKHPLT FGSGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 61 SI-49P2 chain A nt >SEQ ID 62 SI-49P2 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 63 SI-49P2 chain B nt >SEQ ID 64 SI-49P2 chain B aa DIVMTQSPSSLTVTAGEKVTMSC KSSQSLLNSGNQKNYLT WYQQKPGQPPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVQAEDLAVYYC QNDYSYPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRT >SEQ ID 65 SI-49P3 chain A nt >SEQ ID 66 SI-49P3 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGD GFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY LISTEN GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC STYLE DOVE FGCGTKVEIK >SEQ ID 67 SI-49P3 chain B nt >SEQ ID 68 SI-49P3 chain B aa DIQMTQSPSSLSASVGDRVTITC RASQDVNTAVA WYQQKPGKAPKLLIY SASFLYSGVPS RFSGSRSGTDFTLTISSLQPEDFATYYC QQHYTTPPT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 69 SI-49P4 chain A nt >SEQ ID 70 SI-49P4 chain A aa EIVMTQSPSTLSASVGDRVIITC DISCUSSION WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSITE WGQGTLVTVSTGGGGSGGGGSDVQLQESGPSLVKPSQSLSLTCTVTGYSIT SDFA WNWIRQFPGNKLEWMG YISYSGNTRINPSLKS RISITRDTSKNQFFLQLNSVTIEDTATYYCVT AGRGFP YWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 71 SI-49P4 chain B nt >SEQ ID 72 SI-49P4 chain B aa DILMTQSPSSMSVSLGDTVSITC HSSQDINSNIG WLQQRPGKSFKGLIY HGTNLDD EVPSRFSGSGSGADYSLTISSLESEDFADYYC VQYAQFPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 73 SI-49P5 chain A nt >SEQ ID 74 SI-49P5 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGSSVKVSCKASGYTIT DSNIH WVRQAPGQSLEWIG YIYPYNGGTDYNQKFKN RATLTVDNPTNTAYMELSSLRSEDTAFYYCVN GNPWLA YWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHM QWVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 75 SI-49P5 chain B nt >SEQ ID 76 SI-49P5 chain B aa DIQLTQSPSTLSASVGDRVTITC RASESLDNYGIRFLT WFQQKPGKAPKLLMY AASNQGS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQTKEVPWS FGQGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 77 SI-49P6 chain A nt >SEQ ID 78 SI-49P6 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 79 SI-49P6 chain B nt >SEQ ID 80 SI-49P6 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 81 SI-49P7 chain A nt >SEQ ID 82 SI-49P7 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 83 SI-49P7 chain B nt >SEQ ID 84 SI-49P7 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 85 SI-49P10 chain A nt >SEQ ID 86 SI-49P10 chain A aa EIVMTQSPSTLSASVGDRVIITC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKCLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 87 SI-49P10 chain B nt >SEQ ID 88 SI-49P10 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKGSTGSGSKPGSGEGSTKGQVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 97 SI-38E17 chain A nt >SEQ ID 98 SI-38E17 chain A aa >SEQ ID 99 SI-38E17 chain B nt GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 100 SI-38E17 chain B aa AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 105 SI-55H11 chain A nt >SEQ ID 106 SI-55H11 chain A aa >SEQ ID 107 SI-55H11 chain B nt >SEQ ID 108 SI-55H11 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 109 SI-50E1 chain A nt >SEQ ID 110 SI-50E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGDGFYAMD YWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 111 SI-50E1 and SI-50E6 chain B nt GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGGGTCACCATCACCTGCCGTGCCAGTCAGGATGTGAATACTGCTGTAGCCTGGTATCAACAGAAACCAGGAAAAGCTCCGAAACTACTGATTTACTCGGCATCCTTCCTCTACTCTGGAGTCCCTTCTCGCTTCTCTGGCTCCAGATCTGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAGCCGGAAGACTTCGCAACTTATTACTGTCAGCAACATTATACTACTCCTCCCACGTTCGGACAGGGTACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 112 SI-50E1 and SI-50E6 chain B aa DIQMTQSPSSLSASVGDRVTITC RASQDVNTAVA WYQQKPGKAPKLLIY SASFLYS GVPSRFSGSRSGTDFTLTISSLQPEDFATYYC QQHYTTPPT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 113 SI-50E6 chain A nt >SEQ ID 114 SI-50E6 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFNIK DTYIH WVRQAPGKGLEWVA RIYPTNGYTRYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCSR WGGDGFYAMDY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 115 SI-50E2 chain A nt >SEQ ID 116 SI-50E2 chain A aa >SEQ ID 117 SI-50E2 and SI-50E7 chain B nt GACATCCAGATGACACAATCTCCTAGCAGTCTGAGCGCAAGTGTTGGAGATCGTGTCACCATCACATGCAAGGCCAGCCAGGATGTGAGCATTGGAGTCGCCTGGTATCAGCAGAAACCCGGCAAGGCACCCAAGCTGCTGATCTACTCGGCCAGTTACAGATACACTGGCGTACCTTCGAGGTTTAGTGGTAGCGGTTCTGGAACCGATTTCACCCTCACCATTAGCTCCCTCCAACCCGAGGACTTCGCCACCTACTACTGCCAGCAATACTACATCTACCCTTACACGTTCGGCCAAGGCACTAAGGTCGAGATTAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 118 SI-50E2 and SI-50E7 chain B aa DIQMTQSPSSLSASVGDRVTITC KASQDVSIGVA WYQQKPGKAPKLLIY SASYRYT GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYYIYPYT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 119 SI-50E7 chain A nt >SEQ ID 120 SI-50E7 chain A aa >SEQ ID 122 SI-51E1 chain A aa >SEQ ID 123 SI-51E1 and SI-51E4 chain B nt GACATCGAGCTCACTCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTTACATGCACTGGTACCAGCAGAAGTCAGGCACCTCCCCCAAAAGATGGATTTATGACACATCCAAACTGGCTTCTGGAGTCCCAGGTCGCTTCAGTGGCAGTGGGTCTGGAAACTCTTACTCTCTCACAATCAGCAGCGTGGAGGCTGAAGATGATGCAACTTATTACTGCCAGCAGTGGAGTAAGCACCCTCTCACGTTCGGATCCGGGACCAAGGTGGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 124 SI-51E1 and SI-51E4 chain B aa DIELTQSPAIMSASPGEKVTMTC SASSSVSYMH WYQQKSGTSPKRWIY DTSKLAS GVPGRFSGSGSGNSYSLTISSVEAEDDATYYC QQWSKHPLT FGSGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 125 SI-51E4 chain A nt >SEQ ID 126 SI-51E4 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGPELEKPGASVKISCKASGYSFT GYTMN WVKQSHGKSLEWIG LITPYNGASSYNQKFRG KATLTVDKSSSTAYMDLLSLTSEDSAVYFCAR GGYDGRGFDY WGSGTPVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 128 SI-52E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLLQSGPELEKPGASVMISCKASGSSFT GYNMN WVRQNIGKSLEWIG AIDPYYGGTSYNQKFKG RATLTVDKSSSTAYMHLKSLTSEDSAVYYCVS GMEY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 129 SI-52E1 and SI-52E4 chain B nt GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCAGATCTAGTCAGAGTCTTGTACACCGTAATGGAAACACCTATTTACATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATTCACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGTTCTCAAAGTACACATGTTCCTCCGCTCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 130 SI-52E1 and SI-52E4 chain B aa EIVMTQSPATLSVSPGERATLSC RSSQSLVH RNGNTYLHWYLQKPGQSPKLLIH KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDLGVYFC SQSTHVPPLT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 131 SI-52E4 chain A nt >SEQ ID 132 SI-52E4 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLLQSGPELEKPGASVMISCKASGSSFT GYNMN WVRQNIGKSLEWIG AIDPYYGGTSYNQKFKG RATLTVDKSSSTAYMHLKSLTSEDSAVYYCVS GMEY WGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 133 SI-53E1 chain A nt >SEQ ID 134 SI-53E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 135 SI-53E1 and SI-53E3 chain B nt GACATTGTGATGACACAGTCTCCATCCTCCCTGACTGTGACAGCAGGAGAGAAGGTCACTATGAGCTGCAAGTCCAGTCAGAGTCTGTTAAACAGTGGAAATCAAAAGAACTACTTGACCTGGTACCAGCAGAAACCAGGGCAGCCTCCTAAACTGTTGATCTACTGGGCATCCACTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGTGCAGGCTGAAGACCTGGCAGTTTATTACTGTCAGAATGATTATAGTTATCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 136 SI-53E1 and SI-53E3 chain B aa DIVMTQSPSSLTVTAGEKVTMSC KSSQSLLNSGNQKNYLT WYQQKPGQPPKLLIY WASTRES GVPDRFTGSGSGTDFTLTISSVQAEDLAVYYC QNDYSYPFT FGSGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 137 SI-53E3 chain A nt >SEQ ID 138 SI-53E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVRPGASVKLSCKASGYTFT SYWIN WVKQRPGQGLEWIG NIYPSDSYTNYNQKFKD KATLTVDKSSSTAYMQLSSPTSEDSAVYYCTR SWRGNSFDY WGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 139 SI-54E1 chain A nt >SEQ ID 140 SI-54E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFT SYNMH WVKQTPGRGLEWIG AIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR STYYGGDWYFNV WGAGTTVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 141 SI-54E1 and SI-54E3 chain B nt CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGGTGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 142 SI-54E1 and SI-54E3 chain B aa QIVLSQ SPAILSASPG EKVTMTC RASSSVSYIH WFQQKPGSSPKPWIY ATSNLAS GVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 143 SI-54E3 chain A nt >SEQ ID 144 SI-54E3 chain A aa >SEQ ID 145 SI-55E1 chain A nt >SEQ ID 146 SI-55E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 147 SI-55E1 and SI-55E8 chain B nt GACATCTTGCTGACTCAGTCTCCAGTCATCCTGTCTGTGAGTCCAGGAGAAAGAGTCAGTTTCTCCTGCAGGGCCAGTCAGAGTATTGGCACAAACATACACTGGTATCAGCAAAGAACAAATGGTTCTCCAAGGCTTCTCATAAAGTATGCTTCTGAGTCTATCTCTGGGATTCCTTCCAGGTTTAGTGGCAGTGGATCAGGGACAGATTTTACTCTTAGCATCAACAGTGTGGAGTCTGAAGATATTGCAGATTATTACTGTCAACAAAATAATAACTGGCCAACCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 148 SI-55E1 and SI-55E8 chain B aa DILLTQSPVILSVSPGERVSFSC RASQSIGTNIH WYQQRTNGSPRLLIK YES GIPSRFSGSGSGTDFTLSINSVESEDIADYYC QQNNNWPTT FGAGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 149 SI-55E8 chain A nt >SEQ ID 150 SI-55E8 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLKQSGPGLVQPSQSLSITCTVSGFSLT NYGVH WVRQSPGKGLEWLG VIWSGGNTDYNTPFTS RLSINKDNSKSQVFFKMNSLQSNDTAIYYCAR ALTYYDYEFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 151 SI-55E2 chain A nt >SEQ ID 152 SI-55E2 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 153 SI-55E2 and SI-55E9 chain B nt GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 154 SI-55E2 and SI-55E9 chain B aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 155 SI-55E9 chain A nt >SEQ ID 156 SI-55E9 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 157 SI-55E3 chain A nt >SEQ ID 158 SI-55E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QUEEN OF THE DAY WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFT NYYYYY WVRQAPGQGLEWIG GINPTSGGSNFNEKFKT RVTITADESSTTAYMELSSLRSEDTAFYFCTR QGLWFDSDGRGFDF WGQGTTVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY CASTLE GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 159 SI-55E3 and SI-55E10 chain B nt GATATTCAAATGACTCAATCTCCTTCTTCTCTTTCTGCTTCTGTTGGTGATCGTGTTACTATTACTTGTCGTTCTTCTCAAAATATTGTTCATTCTAATGGTAATACTTATCTTGATTGGTATCAACAAACTCCTGGTAAAGCTCCTAAACTTCTTATTTATAAAGTTTCTAATCGTTTTTCTGGTGTTCCTTCTCGTTTTTCTGGTTCTGGTTCTGGTACTGATTTTACTTTTACTATTTCTTCTCTTCAACCTGAAGATATTGCTACTTATTATTGTTTTCAATATTCTCATGTTCCTTGGACTTTTGGTCAAGGTACTAAACTTCAAATTACTCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 160 SI-55E3 and SI-55E10 chain B aa DIQMTQSPSSLSASVGDRVTITC RSSQNIVHSNGNTYLD WYQQTPGKAPKLLIY KVSNRFS GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC FQYSHVPWT FGQGTKLQITRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 161 SI-55E10 chain A nt >SEQ ID 162 SI-55E10 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFT NYYIY WVRQAPGQGLEWIG GINPTSGGSNFNEKFKT RVTITADESSTTAYMELSSLRSEDTAFYFCTR QGLWFDSDGRGFDF WGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 163 SI-56E1 chain A nt >SEQ ID 164 SI-56E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGASVKVSCKASGYRFT NYWIH WVRQAPGQGLEWIG GINPGNNYATYRRKFQG RVTMTADTSTSTVYMELSSLRSEDTAVYYCTR EGYGNYGAWFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 165 SI-56E1 and SI-56E3 chain B nt GACGTTCAAGTGACCCAGAGCCCATCCAGCCTGAGCGCATCTGTAGGAGACCGGGTCACCATCACTTGTAGATCCAGTCAGAGTCTTGCAAACAGTTATGGGAACACCTTTTTGTCTTGGTATCTGCACAAACCAGGTAAAGCCCCACAATTGCTCATCTACGGAATCTCTAACAGATTTAGTGGTGTACCAGACAGGTTCAGCGGTTCCGGAAGTGGTACTGATTTCACCCTCACGATCTCGTCTCTCCAGCCAGAAGATTTCGCCACTTATTACTGTTTACAAGGTACACATCAGCCGTACACATTCGGTCAGGGTACTAAAGTAGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 166 SI-56E1 and SI-56E3 chain B aa DVQVTQSPSSLSASVGDRVTITC RSSQSLANSYGNTFLS WYLHKPGKAPQLLIY GISNRFS GVPDRFSGSGSGTDFTLTISS LQPEDFATYYCLQGTHQPYT FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 167 SI-56E3 chain A nt >SEQ ID 168 SI-56E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSEVQLVQSGAEVKKPGASVKVSCKASGYRFT NYWIH WVRQAPGQGLEWIG GINPGNNYATYRRKFQG RVTMTADTSTSTVYMELSSLRSEDTAVYYCTR EGYGNYGAWFAY WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 169 SI-57E1 chain A nt >SEQ ID 170 SI-57E1 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMSW VRQAPGKGLEWIG VITGRDITYYASWAK GRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQIQLQQSGPEVVKPGASVKISCKASGYTFT DYYIT WVKQKPGQGLE WIGWIYPGSGNTKYNEKFKG KATLTVDTSSSTAFMQLSSLTSEDTAVYFCAN YGNYWFAY WGQGTQVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLNWYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPMW GQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 171 SI-57E1 and SI-57E3 chain B nt GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTTTGATGGTGATAGTTATATGAACTGGTACCAACAGAAACCAGGACAGCCACCCAAAGTCCTCATCTATGCTGCATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTTAG >SEQ ID 172 SI-57E1 and SI-57E3 chain B aa DIVLTQSPASLAVSLGQRATISC KASQSVDFDGDSYM NWYQQKPGQPPKVLIY AASNLES GIPARFSGSGSGTDFTLNIHPVEEEDAATYYC QQSNEDPWT FGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 173 SI-57E3 chain A nt >SEQ ID 174 SI-57E3 chain A aa DVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGCGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKCLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSQIQLQQSGPEVVKPGASVKISCKASGYTFT DYYIT WVKQKPGQGLE WIGWIYPGSGNTKYNEKFKG KATLTVDTSSSTAFMQLSSLTSEDTAVYFCAN YGNYWFAY WGQGTQVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLSW YQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 175 SI-1H1 chain A nt >SEQ ID 176 SI-1H1 chain A aa DIQMTQSPSSLSASVGDRVTITC QASQDISNYLN WYQQKPGKAPKLLIY DASNLET GVPSRFSGSGSGTDFTFTISSLQPEDIATYFC QHFDHLPLA FGGGTKVEIKGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGGSVS SGDYYWT WIRQSPGKGLEWIG HIYYSGNTNYNPSLKS RLTISIDTSKTQFSLKLSSVTAADTAIYYCVR DRVTGAFDI WGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTIS TNAMS WVRQAPGKGLEWIG VITGRDITYYASWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKGLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKGLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGGGTKVEIK >SEQ ID 177 SI-1H1 chain B nt >SEQ ID 178 SI-1H1 chain B aa QSALTQPASVSGSPGQSITISC TGTSSDVGGYNFVS WYQQHPGKAPKLMIY DVSDRPS GVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGS SSTHVI FGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLRLSCAASGFTFS SYWMS WVRQAPGKGLEWVA NINRDGSASYYVDSVKG RFTISRDDAKNSLYLQMNSLRAEDTAVYYCAR DRGVGYFDL WGRGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINC QASESISSWLA WYQQKPGKAPKLLIY EASKLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QGYFYFISRTYVNS FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLS TSGMGVG WIRQPPGKGLEWLA HIWWDDDKRYNPALKS RLTISKDTSKNQVYLQMNSLDAEDTAVYYCAR MELWSYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIK >SEQ ID 183 SI-49R19 chain A nt >SEQ ID 184 SI-49R19 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >SEQ ID 185 SI-49R19 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 186 SI-49R19 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 187 SI-49R18 chain A nt >SEQ ID 188 SI-49R18 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG >SEQ ID 189 SI-49R18 chain B nt >SEQ ID 190 SI-49R18 chain B aa ENVLTQSPASLSASPGERVTITC SASSSVSYMH WYQQKPGQAPKLWIY DTSKLAS GVPSRFSGSGSGNDHTLTISSMEPEDFATYYC FQGSVYPFT FGQGTKLEIKGSTGSGSKPGSGEGSTKGQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 191 SI-49E15 chain A nt >SEQ ID 192 SI-49E15 chain A aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKLTVLGSTGSGSKPGSGEGSTKGEVQLVESGGGLVQPGGSLRLSCTASGFTIS TNAMS WVRQAPGKCLEWVG VITGRDITYYASWAKG RFTISRDTSKNTVYLQMNSLRAEDTAVYYCAR DGGSSAITSNNI WGQGTLVTVSTGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFS SGYDMC WVRQAPGKCLEWIA CIAAGSAGITYDANWAKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR SAFSFDYAMDL WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITC QASQSISSHLN WYQQKPGKAPKLLIY KASTLAS GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQGYSWGNVDNV FGCGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTIS SYHMQ WVRQAPGKCLEYIG TISSGGNVYYASSARG RFTISRPSSKNTVDLQMNSLRAEDTAVYYCAR DSGYSDPM WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITC QASQNIRTYLS WYQQKPGKAPKLLIY AAANLAS GVPSRFSGSGSGTDFTLTISDLEPGDAATYYC QSTYLGTDYVGGA FGCGTKVEIK >SEQ ID 193 SI-49E15 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 194 SI-49E15 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 195 SI-49R21 chain A nt >SEQ ID 196 SI-49R21 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 197 SI-49R21 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 198 SI-49R21 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 199 SI-49R22 chain A nt >SEQ ID 200 SI-49R22 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 201 SI-49R22 chain B nt TTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTGCATGCAAAGGACTGTGCGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT >SEQ ID 202 SI-49R22 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 203 SI-49R22 chain C nt >SEQ ID 204 SI-49R22 chain C aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 205 SI-49R23 chain A nt >SEQ ID 206 SI-49R23 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 207 SI-49R24 chain A nt >SEQ ID 208 SI-49R24 chain A aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 209 SI-49R24 chain B nt >SEQ ID 210 SI-49R24 chain B aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVASEPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK >SEQ ID 217 anti-claudin zolbetuximab VH nt CAGGTCCAACTGCAGCAGCCTGGGGCTGAGCTGGTGAGGCCTGGGGCTTCAGTGAAGCTGTCCTGCAAGGCTTCTGGCTACACCTTCACCAGCTACTGGATAAACTGGGTGAAGCAGAGGCCTGGACAAGGCCTTGAGTGGATCGGAAATATTTATCCTTCTGATAGTTATACTAACTACAATCAAAAGTTCAAGGACAAGGCCACATTGACTGTAGACAAATCCTCCAGCACAGCCTACATGCAGCTCAGCAGCCCGACATCTGAGGACTCTGCGGTCTATTACTGTACAAGATCGTGGAGGGGTAACTCCTTTGACTACTGGGGCCAAGGCACCACTCTCACAGTCTCCTCA >SEQ ID 218 anti-claudin zolbetuximab VH aa QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWINWVKQRPGQGLEWIGNIYPSDSYTNYNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCTRSWRGNSFDYWGQGTTLTVSS >SEQ ID 219 anti-claudin zolbetuximab VL nt GACATTGTGATGACACAGTCTCCATCCTCCCTGACTGTGACAGCAGGAGAGAAGGTCACTATGAGCTGCAAGTCCAGTCAGAGTCTGTTAAACAGTGGAAATCAAAAGAACTACTTGACCTGGTACCAGCAGAAACCAGGGCAGCCTCCTAAACTGTTGATCTACTGGGCATCCACTAGGGAATCTGGGGTCCCTGATCGCTTCACAGGCAGTGGATCTGGAACAGATTTCACTCTCACCATCAGCAGTGTGCAGGCTGAAGACCTGGCAGTTTATTACTGTCAGAATGATTATAGTTATCCATTCACGTTCGGCTCGGGGACAAAGTTGGAAATAAAA >SEQ ID 220 anti-claudin zolbetuximab VL aa DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPFTFGSGTKLEIK >SEQ ID 221 anti-HER2 trastuzumab VH nt GAGGTTCAGCTGGTGGAGTCTGGCGGTGGCCTGGTGCAGCCAGGGGGCTCACTCCGTTTGTCCTGTGCAGCTTCTGGCTTCAACATTAAAGACACCTATATACACTGGGTGCGTCAGGCCCCGGGTAAGGGCCTGGAATGGGTTGCAAGGATTTATCCTACGAATGGTTATACTAGATATGCCGATAGCGTCAAGGGCCGTTTCACTATAAGCGCAGACACATCCAAAAACACAGCCTACCTGCAGATGAACAGCCTGCGTGCTGAGGACACTGCCGTCTATTATTGTTCTAGATGGGGAGGGGACGGCTTCTATGCTATGGACTACTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCG >SEQ ID 222 anti-HER2 trastuzumab VH aa EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS >SEQ ID 223 anti-HER2 trastuzumab VL nt GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGGGTCACCATCACCTGCCGTGCCAGTCAGGATGTGAATACTGCTGTAGCCTGGTATCAACAGAAACCAGGAAAAGCTCCGAAACTACTGATTTACTCGGCATCCTTCCTCTACTCTGGAGTCCCTTCTCGCTTCTCTGGCTCCAGATCTGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAGCCGGAAGACTTCGCAACTTATTACTGTCAGCAACATTATACTACTCCTCCCACGTTCGGACAGGGTACCAAGGTGGAGATCAAA >SEQ ID 224 anti-HER2 trastuzumab VL aa DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >SEQ ID 225 anti-HER2 pertuzumab VH nt GAAGTGCAGCTCGTCGAAAGCGGTGGCGGACTGGTTCAGCCCGGTGGTTCTCTGCGGCTGTCTTGTGCTGCCTCGGGTTTCACGTTCACTGACTACACAATGGACTGGGTGCGTCAGGCTCCTGGAAAGGGATTGGAGTGGGTAGCCGACGTTAATCCAAACTCCGGCGGGAGCATCTACAACCAGAGGTTCAAGGGGAGGTTCACTCTGAGCGTGGATCGCTCCAAGAACACGCTGTACCTCCAGATGAACTCTCTCAGGGCCGAGGACACGGCTGTTTACTATTGCGCGAGGAACCTGGGTCCTTCCTTCTACTTCGACTACTGGGGACAGGGAACCCTGGTGACCGTCAGCTCC >SEQ ID 226 anti-HER2 pertuzumab VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS >SEQ ID 227 anti-HER2 pertuzumab VL nt GACATCCAGATGACACAATCTCCTAGCAGTCTGAGCGCAAGTGTTGGAGATCGTGTCACCATCACATGCAAGGCCAGCCAGGATGTGAGCATTGGAGTCGCCTGGTATCAGCAGAAACCCGGCAAGGCACCCAAGCTGCTGATCTACTCGGCCAGTTACAGATACACTGGCGTACCTTCGAGGTTTAGTGGTAGCGGTTCTGGAACCGATTTCACCCTCACCATTAGCTCCCTCCAACCCGAGGACTTCGCCACCTACTACTGCCAGCAATACTACATCTACCCTTACACGTTCGGCCAAGGCACTAAGGTCGAGATTAAA >SEQ ID 228 anti-HER2 pertuzumab VL aa DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIK >SEQ ID 229 anti-mesothelin amatuximab VH nt CAGGTACAACTGCAGCAGTCTGGGCCTGAGCTGGAGAAGCCTGGCGCTTCAGTGAAGATATCCTGCAAGGCTTCTGGTTACTCATTCACTGGCTACACCATGAACTGGGTGAAGCAGAGCCATGGAAAGAGCCTTGAGTGGATTGGACTTATTACTCCTTACAATGGTGCTTCTAGCTACAACCAGAAGTTCAGGGGCAAGGCCACATTAACTGTAGACAAGTCATCCAGCACAGCCTACATGGACCTCCTCAGTCTGACATCTGAAGACTCTGCAGTCTATTTCTGTGCAAGGGGGGGTTACGACGGGAGGGGTTTTGACTACTGGGGATCTGGGACCCCGGTCACCGTCTCCTCA >SEQ ID 230 anti-mesothelin amatuximab VH aa QVQLQQSGPELEKPGASVKISCKASGYSFTGYTMNWVKQSHGKSLEWIGLITPYNGASSYNQKFRGKATLTVDKSSSTAYMDLLSLTSEDSAVYFCARGGYDGRGFDYWGSGTPVTVSS >SEQ ID 231 anti-mesothelin amatuximab VL nt GACATCGAGCTCACTCAGTCTCCAGCAATCATGTCTGCATCTCCAGGGGAGAAGGTCACCATGACCTGCAGTGCCAGCTCAAGTGTAAGTTACATGCACTGGTACCAGCAGAAGTCAGGCACCTCCCCCAAAAGATGGATTTATGACACATCCAAACTGGCTTCTGGAGTCCCAGGTCGCTTCAGTGGCAGTGGGTCTGGAAACTCTTACTCTCTCACAATCAGCAGCGTGGAGGCTGAAGATGATGCAACTTATTACTGCCAGCAGTGGAGTAAGCACCCTCTCACGTTCGGATCCGGGACCAAGGTGGAAATCAAA >SEQ ID 232 anti-mesothelin amatuximab VL aa DIELTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASGVPGRFSGSGSGNSYSLTISSVEAEDDATYYCQQWSKHPLTFGSGTKVEIK >SEQ ID 233 anti-GD2 dinutuximab VH nt GAGGTCCAACTGCTGCAGTCTGGACCTGAGCTGGAGAAGCCTGGCGCTTCAGTGATGATATCCTGCAAGGCTTCTGGTTCCTCATTCACTGGCTACAACATGAACTGGGTGAGGCAGAACATTGGAAAGAGCCTTGAATGGATTGGAGCTATTGATCCTTACTATGGTG GAACTAGCTACAACCAGAAGTTCAAGGGCAGGGCCACATTGACTGTAGACAAATCGTCCAGCAGCCTACATGCACCTCAAGAGCCTGACATCTGAGGACTCTGCAGTCTATTACTGTGTAAGCGGAATGGAGTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCCA >SEQ ID 234 anti-GD2 dinutuximab VH aa EVQLLQSGPELEKPGASSVMISCKASGSSFTGYNMNWVRQNIGKSLEWIGAIDPYYGGTSYNQKFKGRATLTVDKSSSTAYMHLKSLTSEDSAVYYCVSGMEYWGQGTSVTVSS >SEQ ID 235 anti-GD2 dinutuximab VL nt GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTGTGTCTCCAGGGGAAAGCCACCCTCTCCTGCAGATCTAGTCAGAGTCTTGTACACCGTAATGGAAACACCTATTTATTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGCTCCTGATTCACAAAGTTT CCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATCTGTTCTCAAAGTACACATGTTCCTCCGCTCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAA >SEQ ID 236 anti-GD2 dinutuximab VL aa EIVMTQSPATLSVSPGERATLSCRSSQSLVHRNGNTYLHWYLQKPGQSPKLLIHKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPPLTFGAGTKLELK >SEQ ID 237 anti-CD20 rituximab VH nt CAGGGTGCAGCTGCAGCAGCCCGGCGCCGAGCTGGTGAAGCCCGGCGCCAGCGTGAAGATGAGCTGCAAGGCCAGCGGCTACACCTTCACCAGCTACAACATGCACTGGGTGAAGCAGACCCCCGGCCGGGGCCTGGAGTGGATCGGGCCATCTACCCCGGCAACGGCGACACCAGCTACA ACCAGAAGTTCAAGGGCAAGGCCACCCTGACCGCCGACAAGAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACCAGCGAGGACAGCGCCGTGTACTACTGCGCCCGGGAGCACCTACTACGGCGGCGACTGGTACTTCAACGTGTGGGGCGCCGGCACCACCGTGACCGTGAGCGCC >SEQ ID 238 anti-CD20 rituximab VH aa QVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSA >SEQ ID 239 anti-CD20 rituximab VL nt CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGGTGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGGAGATCAAG >SEQ ID 240 anti-CD20 rituximab VL aa QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIK >SEQ ID 241 anti-EGFR cetuximab VH nt CAGGTGCAGCTGAAGCAGTCAGGACCTGGCCTAGTGCAGCCCTCACAGAGCCTGTCCATCACCTGCACAGTCTCTGGTTTCTCATTAACTAACTATGGTGTACACTGGGTTCGCCAGTCTCCAGGAAAGGGTCTGGAGTGGCTGGGAGTGATATGGAGTGGTGGAAACACAGACTATAATACACCTTTCACATCCAGACTGAGCATCAACAAGGACAATTCCAAGAGCCAAGTTTTCTTTAAAATGAACAGTCTGCAATCTAATGACACAGCCATATATTACTGTGCCAGAGCCCTCACCTACTATGATTACGAGTTTGCTTACTGGGGCCAAGGGACTCTGGTCACTGTCTCTAGC >SEQ ID 242 anti-EGFR cetuximab VH aa QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSS >SEQ ID 243 anti-EGFR cetuximab VL nt GACATCTTGCTGACTCAGTCTCCAGTCATCCTGTCTGTGAGTCCAGGAGAAAGAGTCAGTTTCTCCTGCAGGGCCAGTCAGAGTATTGGCACAAACATACACTGGTATCAGCAAAGAACAAATGGTTCTCCAAGGCTTCTCATAAAGTATGCTTCTGAGTCTATCTCTGGGATTCCTTCCAGGTTTAGTGGCAGTGGATCAGGGACAGATTTTACTCTTAGCATCAACAGTGTGGAGTCTGAAGATATTGCAGATTATTACTGTCAACAAAATAATAACTGGCCAACCACGTTCGGTGCTGGGACCAAGCTGGAGCTGAAA >SEQ ID 244 anti-EGFR cetuximab VL aa DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELK >SEQ ID 245 anti-EGFR panitumumab VH nt CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCGTCAGCAGTGGTGATTACTACTGGACCTGGATCCGGCAGTCCCCAGGGAAGGGACTGGAGTGGATTGGACACATCTATTACAGTGGGAACACCAATTATAACCCCTCCCTCAAGAGCCGACTCACCATATCAATTGACACGTCCAAGACTCAGTTCTCCCTGAAGCTGAGTTCTGTGACCGCTGCGGACACGGCCATTTATTACTGTGTGCGAGATCGAGTGACTGGTGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCGAGC >SEQ ID 246 anti-EGFR panitumumab VH aa QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGDYYWTWIRQSPGKGLEWIGHIYYSGNTNYNPSLKSRLTISIDTSKTQFSLKLSSVTAADTAIYYCVRDRVTGAFDIWGQGTMVTVSS >SEQ ID 247 anti-EGFR panitumumab VL nt GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCGAGTCAGGACATCAGCAACTATTTAAATTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGCAACATATTTCTGTCAACACTTTGATCATCTCCCGCTCGCTTTCGGCGGAGGGACCAAGGTGGAAATTAAA >SEQ ID 248 anti-EGFR panitumumab VL aa DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYFCQHFDHLPLAFGGGTKVEIK >SEQ ID 249 anti-EGFR nimotuzumab VH nt CAGGGTGCAGCTGCAGCAGAGCGGCGCCGAGGTGAAGAAGCCCGGCAGCAGCGTGAAGGTGAGCTGCAAGGCCAGCGGCTACACCTTCACCAACTACATCTACTGGGTGCGGCAGGCCCCGGCAGGGCCTGGAGTGGATCGGCGCATCAACCCCACCAGCGGCGGCAGCAACTTCAACG AGAAGTTCAAGACCCGGGTGACCATCACCGCCGACGAGAGCAGCACCACCGCCTACATGGAGCTGAGCAGCCTGCGGAGCGAGGACACCGCCTTCTACTTCTGCACCCGGCAGGGCCTGTGGTTCGACAGCGACGGCCGGGGCTTCGACTTCTGGGGCCAGGGCACCACCGTGACCGTGAGCAGC >SEQ ID 250 anti-EGFR nimotuzumab VH aa QVQLQQSGAEVKKPGSSVKVSCKASGYTFTNYYIYWVRQAPGQGLEWIGGINPTSGGSNFNEKFKTRVTITADESSTTAYMELSSLRSEDTAFYFCTRQGLWFDSDGRGFDFWGQGTTVTVSS >SEQ ID 251 anti-EGFR nimotuzumab VL nt GATATTCAAATGACTCAATCTCCTTCTTCTCTTTCTGCTTCTGTTGGTGATCGTGTTACTATTACTTGTCGTTCTTCTCAAAATATTGTTCATTCTAATGGTAATACTTATCTTGATTGGTATCAACAAACTCCTGGTAAAGCTCCTAAACTTCTTATTTATAAAGTTTCTAATCGTTTTTCTGGTGTTCCTTCTCGTTTTTCTGGTTCTGGTTCTGGTACTGATTTTACTTTTACTATTTCTTCTCTTCAACCTGAAGATATTGCTACTTATTATTGTTTTCAATATTCTCATGTTCCTTGGACTTTTGGTCAAGGTACTAAACTTCAAATTACT >SEQ ID 252 anti-EGFR nimotuzumab VL aa DIQMTQSPSSLSASVGDRVTITCRSSQNIVHSNGNTYLDWYQQTPGKAPKLLIYKVSNRFSGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCFQYSHVPWTFGQGTKLQIT >SEQ ID 253 anti-CD22 inotuzumab VH nt GAGGTGCAATTGGTCCAGTCAGGAGCAGAGGTTAAGAAGCCTGGTGCTTCCGTCAAAGTTTCGTGTAAGGCCAGCGGCTACAGGTTCACAAATTATTGGATTCATTGGGTCAGGCAGGCTCCGGGACAAGGCCTGGAATGGATCGGTGGCATTAATCCCGGGAATAACTACGCTACATATAGGAGAAAATTCCAGGGCAGAGTTACGATGACCGCGGACACCTCCACAAGCACTGTCTACATGGAGCTGTCATCTCTGAGATCCGAGGACACCGCAGTGTACTATTGTACTAGAGAAGGCTACGGTAATTACGGAGCCTGGTTCGCCTACTGGGGCCAGGGTACCCTAGTCACAGTCTCCTCA >SEQ ID 254 anti-CD22 inotuzumab VH aa EVQLVQSGAEVKKPGASVKVSCKASGYRFTNYWIHWVRQAPGQGLEWIGGINPGNNYATYRRKFQGRVTMTADTSTSTVYMELSSLRSEDTAVYYCTREGYGNYGAWFAYWGQGTLVTVSS >SEQ ID 255 anti-CD22 inotuzumab VL nt GACGTTCAAGTGACCCAGAGCCCATCCAGCCTGAGCGCATCTGTAGGAGACCGGGTCACCATCACTTGTAGATCCAGTCAGAGTCTTGCAAACAGTTATGGGAACACCTTTTTGTCTTGGTATCTGCACAAACCAGGTAAAGCCCCACAATTGCTCATCTACGGAATCTCTAACAGATTTAGTGGTGTACCAGACAGGTTCAGCGGTTCCGGAAGTGGTACTGATTTCACCCTCACGATCTCGTCTCTCCAGCCAGAAGATTTCGCCACTTATTACTGTTTACAAGGTACACATCAGCCGTACACATTCGGTCAGGGTACTAAAGTAGAAATCAAA >SEQ ID 256 anti-CD22 inotuzumab VL aa DVQVTQSPSSLSASVGDRVTITCRSSQSLANSYGNTFLSWYLHKPGKAPQLLIYGISNRFSGVPDRFSGSGSGTDFTLTISSLQPEDFATYYCLQGTHQPYTFGQGTKVEIK >SEQ ID 257 anti-CD30 brentuximab VH nt CAGATCCAGCTGCAGCAGTCTGGACCTGAGGTGGTGAAGCCTGGGGCTTCAGTGAAGATATCCTGCAAGGCTTCTGGCTACACCTTCACTGACTACTATATAACCTGGGTGAAGCAGAAGCCTGGACAGGGACTTGAGTGGATTGGATGGATTTATCCTGGAAGCGGTAATACTAAGTACAATGAGAAGTTCAAGGGCAAGGCCACATTGACTGTAGACACATCCTCCAGCACAGCCTTCATGCAGCTCAGCAGCCTGACATCTGAGGACACTGCTGTCTATTTCTGTGCGAACTATGGTAACTACTGGTTTGCTTACTGGGGCCAAGGGACTCAGGTCACTGTCTCTGCA >SEQ ID 258 anti-CD30 brentuximab VH aa QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKYNEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGNYWFAYWGQGTQVTVSA >SEQ ID 259 anti-CD30 brentuximab VL nt GACATTGTGCTGACCCAATCTCCAGCTTCTTTGGCTGTGTCTCTAGGGCAGAGGGCCACCATCTCCTGCAAGGCCAGCCAAAGTGTTGATTTTGATGGTGATAGTTATATGAACTGGTACCAACAGAAACCAGGACAGCCACCCAAAGTCCTCATCTATGCTGCATCCAATCTAGAATCTGGGATCCCAGCCAGGTTTAGTGGCAGTGGGTCTGGGACAGACTTCACCCTCAACATCCATCCTGTGGAGGAGGAGGATGCTGCAACCTATTACTGTCAGCAAAGTAATGAGGATCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 260 anti-CD30 brentuximab VL aa DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKVLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK >SEQ ID 261 anti-HER3 MM-111 VH nt CAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCGAGC >SEQ ID 262 anti-HER3 MM-111 VH aa QVQLQESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 263 anti-HER3 MM-111 VL nt CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTCTCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTCCTA >SEQ ID 264 anti-HER3 MM-111 VL aa QSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVL >SEQ ID 265 anti-EGFRvIII ABT-806 VH nt GATGTGCAGCTTCAGGAGTCGGGACCTAGCCTGGTGAAACCTTCTCAGTCTCTGTCCCTCACCTGCACTGTCACTGGCTACTCAATCACCAGTGATTTTGCCTGGAACTGGATTCGGCAGTTTCCAGGAAACAAGCTGGAGTGGATGGGCTACATAAGTTATAGTGGTAACACTAGGTACAACCCATCTCTCAAAAGTCGAATCTCTATCACTCGCGACACATCCAAGAACCAATTCTTCCTGCAGTTGAACTCTGTGACTATTGAGGACACAGCCACATATTACTGTGTAACGGCGGGACGCGGGTTTCCTTATTGGGGCCAAGGGACTCTGGTCACTGTCTCTGCA >SEQ ID 266 anti-EGFRvIII ABT-806 VH aa DVQLQESGPSLVKPSQSLSLTCTVTGYSITSDFAWNWIRQFPGNKLEWMGYISYSGNTRYNPSLKSRISITRDTSKNQFFLQLNSVTIEDTATYYCVTAGRGFPYWGQGTLVTVSA >SEQ ID 267 anti-EGFRvIII ABT-806 VL nt GACATCCTGATGACCCAATCTCCATCCTCCATGTCTGTATCTCTGGGAGACACAGTCAGCATCACTTGCCATTCAAGTCAGGACATTAACAGTAATATAGGGTGGTTGCAGCAGAGACCAGGGAAATCATTTAAGGGCCTGATCTATCATGGAACCAACTTGGACGATGAAGTTCCATCAAGGTTCAGTGGCAGTGGATCTGGAGCCGATTATTCTCTCACCATCAGCAGCCTGGAATCTGAAGATTTTGCAGACTATTACTGTGTACAGTATGCTCAGTTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 268 anti-EGFRvIII ABT-806 VL aa DILMTQSPSSMSVSLGDTVSITCHSSQDINSNIGWLQQRPGKSFKGLIYHGTNLDDEVPSRFSGSGSGADYSLTISSLESEDFADYYCVQYAQFPWTFGGGTKLEIK >SEQ ID 269 anti-CD19 21D4 VH nt GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAGAAACCAGGAGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTAGCAGTTCATGGATCGGCTGGGTGCGCCAGGCACCTGGGAAAGGCCTGGAATGGATGGGGATCATCTATCCTGATGACTCTGATACCAGATACAGTCCATCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGGACTGCCTACCTGCAGTGGAGTAGCCTGAAGGCCTCGGACACCGCTATGTATTACTGTGCGAGACATGTTACTATGATTTGGGGAGTTATTATTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA >SEQ ID 270 anti-CD19 21D4 VH aa EVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQAPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSS >SEQ ID 271 anti-CD19 21D4 VL nt GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTTTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAA >SEQ ID 272 anti-CD19 21D4 VL aa AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIK >SEQ ID 273 anti-CD33 gemtuzumab VH nt GAGGTCCAATTGGTACAATCCGGCGCTGAGGTTAAGAAACCGGGTTCCTCAGTCAAAGTTAGTTGTAAGGCATCAGGTTACACGATCACTGATAGTAACATACATTGGGTGAGACAGGCTCCTGGGCAGTCCCTTGAGTGGATTGGATACATTTATCCATATAATGGCGGCACGGATTACAACCAGAAATTTAAGAATAGAGCGACACTGACCGTTGACAACCCCACCAATACCGCGTATATGGAATTGTCAAGCCTGAGGTCTGAGGACACGGCCTTCTACTATTGCGTAAACGGTAACCCGTGGCTGGCCTACTGGGGGCAGGGGACACTCGTAACCGTCTCTTCT >SEQ ID 274 anti-CD33 gemtuzumab VH aa EVQLVQSGAEVKKPGSSVKVSCKASGYTITDSNIHWVRQAPGQSLEWIGYIYPYNGGTDYNQKFKNRATLTVDNPTNTAYMELSSLRSEDTAFYYCVNGNPWLAYWGQGTLVTVSS >SEQ ID 275 anti-CD33 gemtuzumab VL nt GATATACAACTTACGCAGTCTCCCTCCACTCTGTCAGCGTCCGTAGGGGACAGAGTAACGATAACATGCAGGGCCTCAGAAAGTCTTGACAACTACGGCATAAGGTTCCTCACATGGTTTCAACAGAAGCCGGGTAAAGCACCAAAACTCCTGATGTATGCTGCGTCTAACCAGGGGTCCGGTGTTCCTAGTCGGTTTTCAGGCAGCGGTAGCGGTACCGAGTTCACTCTCACAATTTCCAGTCTTCAGCCTGACGATTTCGCAACGTATTATTGCCAACAAACTAAGGAAGTGCCTTGGAGCTTTGGGCAAGGCACCAAGGTCGAGGTGAAG >SEQ ID 276 anti-CD33 gemtuzumab VL aa DIQLTQSPSTLSASVGDRVTITCRASESLDNYGIRFLTWFQQKPGKAPKLLMYAASNQGSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQTKEVPWSFGQGTKVEVK >SEQ ID 277 anti-CD3 284A10 VH nt GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCGACA >SEQ ID 278 anti-CD3 284A10 VH aa EVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVST >SEQ ID 279 anti-CD3 284A10 VL nt GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 280 anti-CD3 284A10 VL aa DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIK >SEQ ID 281 anti-PD-L1 PL221G5 VH nt GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC >SEQ ID 282 anti-PD-L1 PL221G5 VH aa EVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSS >SEQ ID 283 anti-PD-L1 PL221G5 VL nt GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 284 anti-PD-L1 PL221G5 VL aa DIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIK >SEQ ID 285 anti-4-1BB 466F6 VH nt CGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCA >SEQ ID 286 anti-4-1BB 466F6 VH aa RSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYYCARDSGYSDPMWGQGTLVTVSS >SEQ ID 287 anti-4-1BB 466F6 VL nt GACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA >SEQ ID 288 anti-4-1BB 466F6 VL aa DVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK >SEQ ID 289 anti-CD19 SI-BU12 VH nt CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGCCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT >SEQ ID 290 anti-CD19 SI-BU12 VH aa QVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS >SEQ ID 291 anti-CD19 SI-BU12 VL nt GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTGACCGTCCTA >SEQ ID 292 anti-CD19 SI-BU12 VL aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVL >SEQ ID 293 NKG2D nt TTTCTTAATTCCCTTTTCAACCAAGAGGTTCAGATCCCCTTGACTGAAAGCTATTGCGGCCCTTGTCCGAAAAACTGGATATGTTACAAGAATAATTGTTACCAATTCTTCGACGAAAGCAAGAACTGGTATGAGAGTCAGGCGTCTTGTATGAGTCAGAATGCCAGCCTGCTTAAGGTTTATTCAAAAGAAGACCAGGATCTGCTTAAGTTGGTAAAGAGCTACCACTGGATGGGGCTGGTACATATCCCAACGAATGGGTCATGGCAGTGGGAGGACGGTTCTATTCTGAGTCCAAATCTCCTGACGATCATCGAAATGCAGAAAGGGGACTGTGCCCTGTATGCATCATCCTTCAAGGGGTACATCGAGAACTGCAGTACCCCAAATACCTACATTTGTATGCAAAGAACGGTT >SEQ ID 294 NKG2D aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 295 4-1BB ligand nt >SEQ ID 296 4-1BB ligand aa REGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGSTGSGSKPGSGEGSTKGREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLGGGGSGGGGSREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGL >SEQ ID 301 SI-55P9 chain A nt >SEQ ID 302 SI-55P9 chain A aa >SEQ ID 303 SI-55P9 chain B nt >SEQ ID 304 SI-55P9 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 305 SI-55P10 chain A nt >SEQ ID 306 SI-55P10 chain A aa >SEQ ID 307 SI-55P10 chain B nt >SEQ ID 308 SI-55P10 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC >SEQ ID 309 NKG2D dimer nt TTTCTTAATTCCCTTTTCAACCAAGAGGTTCAGATCCCCTTGACTGAAAGCTATTGCGGCCCTTGTCCGAAAAACTGGATATGTTACAAGAATAATTGTTACCAATTCTTCGACGAAAGCAAGAACTGGTATGAGAGTCAGGCGTCTTGTATGAGTCAGAATGCCAGCCTGCTTAAGGTTTATTCAAAAGAAGACCAGGATCTGCTTAAGTTGGTAAAGAGCT ACCACTGGATGGGGCTGGTACATATCCCAACGAATGGGTCATGGCAGTGGGAGGACGGTTCTATTCTGAGTCCAAATCTCCTGACGATCATCGAAATGCAGAAAGGGGACTGTGCCCTGTATGCATCATCCTTCAAGGGGTACATCGAGAACTGCAGTACCCCAAATACCTACATTTGTATGCAAAGAACGGTTGGAGGCGGTGGCTCAGGCGGAGGCGGCTCA GGAGGTGGCGGTTCAGGAGGCGGCGGATCTTTCCTAAACTCATTATTCAACCAAGAAGTTCAAATTCCCTTGACCGAAAGTTACTGTGGCCCATGTCCTAAAAACTGGATATGTTACAAAAATAACTGCTACCAATTTTTTGATGAGAGTAAAAACTGGTATGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGGACCAGGATTTACTTAAACTGGTGAAGTCATATCATTGGATGGGACTAGTACACATTCCAACAATGGATCTTGGCAGTGGGAAGATGGCTCCATTCTCTCACCCAACCTACTAACAATAATTGAAATGCAGAAGGGAGACTGTGCACTCTATGCCTCGAGCTTTAAAGGCTATATAGAAAACTGTTCAACTCCAAATACGTACATCTCCATGCAAAGGACTGTG >SEQ ID 310 NKG2D dimer aa FLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTVGGGGSGGGGSGGGGSGGGGSFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV >SEQ ID 311 anti-FITC 4-4-20 VH nt GAGGTGAAGCTGGATGAGACTGGAGGAGGCTTGGTGCAACCTGGGAGGCCCATGAAACTCTCCTGTGTTGCCTCTGGATTCACTTTTAGTGACTACTGGATGAACTGGGTCCGCCAGTCTCCAGAGAAAGGACTGGAGTGGGTAGCACAAATTAGAAACAAACCTTATAATTATGAAACATATTATTCAGATTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGTAGTGTCTACCTGCAAATGAACAACTTAAGAGTTGAAGACATGGGTATCTATTACTGTACGGGTTCTTACTATGGTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCA >SEQ ID 312 anti-FITC 4-4-20 VH aa EVKLDETGGGLVQPGRPMKLSCVASGFTFSDYWMNWVRQSPEKGLEWVAQIRNKPYNYETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDMGIYYCTGSYYGMDYWGQGTSVTVSS >SEQ ID 313 anti-FITC 4-4-20 VL nt GATGTCGTGATGACCCAAACTCCACTCTCCCTGCCTGTCAGTCTTGGAGATCAAGCCTCCATCTCTTGCAGATCTAGTCAGAGCCTTGTACACAGTAATGGAAACACCTATTTACGTTGGTACCTGCAGAAGCCAGGCCAGTCTCCAAAGGTCCTGATCTACAAAGTTTCCAACCGATTTTCTGGGGTCCCAGACAGGTTCAGTGGCAGTGGATCAGGGACAGATTTCACACTCAAGATCAGCAGAGTGGAGGCTGAGGATCTGGGAGTTTATTTCTGCTCTCAAAGTACACATGTTCCGTGGACGTTCGGTGGAGGCACCAAGCTGGAAATCAAA >SEQ ID 314 anti-FITC 4-4-20 VL aa DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLRWYLQKPGQSPKVLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPWTFGGGTKLEIK >SEQ ID 315 anti-CD3 284A10 FR 1 VH nt GAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCTTCACCATCAGCACCAACGCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGGGCGTGATCACCGGCAGGGACATCACCTACTACGCCAGCTGGGCCAAGGGCAGGTTCACCATCAGCAGGGACACCAGCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGGGACGGCGGCAGCAGCGCCATCACCAGCAACAACATCTGGGGCCAGGGCACCCTGGTGACCGTGAGCAGC >SEQ ID 316 anti-CD3 284A10 FR 1 VH aa EVQLVESGGGLVQPGGSLRLSCTASGFTISTNAMSWVRQAPGKGLEWVGVITGRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSS >SEQ ID 317 anti-CD3 284A10 FR 1 VL nt GAGATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCAGCGTGGGCGACAGGGTGATCATCACCTGCCAGGCCAGCGAGAGCATCAGCAGCTGGCTGGCCTGGTACCAGCAGAAGCCCGGCAAGGCCCCCAAGCTGCTGATCTACGAGGCCAGCAAGCTGGCCAGCGGCGTGCCCAGCAGGTTCAGCGGCAGCGGCAGCGGCGCCGAGTTCACCCTGACCATCAGCAGCCTGCAGCCCGACGACTTCGCCACCTACTACTGCCAGGGCTACTTCTACTTCATCAGCAGGACCTACGTGAACAGCTTCGGCCAGGGCACCAAGCTGACCGTGCTG >SEQ ID 318 anti-CD3 284A10 FR 1 VL aa EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVL >SEQ ID 319 anti-EGFR H7 VH nt CAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGCTTTAGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAAGGTTTGGAATGGCTGGGTGTTATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACGATTACGAATTTGCGTATTGGGGGCAAGGGACTCTTGTAACAGTCTCGAGC >SEQ ID 320 anti-EGFR H7 VH aa QVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSS >SEQ ID 321 anti-EGFR H7 VL nt GAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCGGCGAACGCGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTTCTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTAGTGTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGACCCGGTACAAAGCTGACCGTTTTA >SEQ ID 322 anti-EGFR H7 VL aa EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVL >SEQ ID 323 SI-77H4 chain A nt >SEQ ID 324 SI-77H4 chain A aa >SEQ ID 325 SI-77H4 chain B nt >SEQ ID 326 SI-77H4 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGCGTKLTVLRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 327 SI-77H5 chain A nt >SEQ ID 328 SI-77H5 chain A aa >SEQ ID 329 SI-77H5 chain B nt >SEQ ID 330 SI-77H5 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGCGTKLELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS >SEQ ID 331 SI-55H12 chain A nt >SEQ ID 332 SI-55H12 chain A aa >SEQ ID 333 SI-55H12 chain B nt >SEQ ID 334 SI-55H12 chain B aa ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRFSGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFTFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS

Claims

1. A hexabody-like protein, comprising: having an N-terminus and a C-terminus, and arranged in series from the N-terminus to the C-terminus, a first binding domain (D1) at the N-terminus; a Fab region comprising a light chain as the second binding domain (D2), Fc region, A third binding domain (D3) having binding affinity for PD-L1, and a fourth binding domain (D4) at the C-terminus having binding affinity for 4-1BB; Including, the light chain comprises a fifth binding domain (D5) covalently attached to its C-terminus and a sixth binding domain (D6) covalently attached to its N-terminus; D1, D2, D5 and D6 are hexaspecific antibody-like proteins each independently having binding affinity for a tumor-associated antigen (TAA) or CD3.

2. The hexaspecific antibody-like protein of claim 1 , wherein D1 or D2 has binding affinity for CD3.

3. 2. The multispecific antibody-like protein of claim 1, comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 176, 178, 106, 108, 332, 334, 324, 326, 328 or 330.

4. The multispecific antibody-like protein of claim 1 , wherein D1, D3, D4, D5 and D6 are each independently an scFv domain, a receptor or a ligand.

5. 2. The multispecific antibody monomer of claim 1, wherein D1 has binding specificity for CD3, D2 has binding specificity for EGFR, EGFRvIII, CD20, mesothelin, claudin 18.2, HER2, CD33 or a combination thereof, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, and D5 and D6 each independently have binding specificity for a tumor associated antigen.

6. 2. The multispecific antibody monomer of claim 1, wherein D1 has binding specificity for CD3, D2 has binding specificity for a tumor associated antigen, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, and D5 and D6 each independently have binding specificity for a NKG2D ligand, HER3, CD19, or a combination thereof.

7. 2. The multispecific antibody-like protein of claim 1, wherein D1 has binding specificity for EGFR, D2 has binding specificity for CD3, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, D5 has binding specificity for CD19, and D6 has binding specificity for HER3.

8. 2. The multispecific antibody-like protein of claim 1, wherein D1 has binding specificity for EGFR, D2 has binding specificity for CD3, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, D5 has binding specificity for HER3, and D6 has binding specificity for CD19.

9. 2. The multispecific antibody-like protein of claim 1, wherein the D1 has binding specificity for CD3, the D2 has binding specificity for EGFR, the D3 has binding specificity for PD-L1, the D4 has binding specificity for 4-1BB, the D5 has binding specificity for HER3, and the D6 has binding specificity for CD19.

10. A multispecific antibody-like protein, comprising: having an N-terminus and a C-terminus, and arranged in series from the N-terminus to the C-terminus, a first binding domain (D1) at the N-terminus; a Fab region comprising a light chain as a second binding domain (D2), said light chain optionally comprising a fifth binding domain (D5) covalently attached to the C-terminus and a sixth binding domain (D6) covalently attached to the N-terminus, Fc region, A third binding domain (D3), and a fourth binding domain (D4) at the C-terminus; Including, The multispecific antibody-like proteins are selected from the group consisting of SEQ ID NOs: 110, 112, 116, 118, 122, 124, 128, 130, 134, 136, 140, 142, 146, 148, 152, 154, 158, 160, 164, 166, 170, 172, 112, 114, 118, 120, 124, 126, 130, 132, 136, 1 38, 142, 144, 148, 150, 154, 156, 160, 162, 166, 168, 172, 174, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 302, 304, 306 or 308.

11. The multispecific antibody-like protein of claim 10, wherein D2, D5 and D6 each independently have binding affinity for a tumor-associated antigen (TAA).

12. 11. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for CD3, D2 has binding specificity for a tumor associated antigen, D3 has binding specificity for PD-L1, and D4 has binding specificity for 4-1BB.

13. 11. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for CD3, D2 has binding specificity for an antigen selected from the group consisting of EGFR, HER2, CD19, CD20, CD22, CD30, CD22, mesothelin, GD2 and claudin 18.2, D3 has binding specificity for PD-L1, and D4 has binding specificity for 4-1BB.

14. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for CD3, D2 and D5 each independently have binding specificity for a tumor associated antigen, D3 has binding specificity for PD-L1, and D4 has binding specificity for 4-1BB.

15. 11. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for CD3, D2 has binding specificity for a tumor associated antigen, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, and D5 has binding specificity for HER3.

16. 11. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for CD3, D2 has binding specificity for EGFR or EGFRvIII, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, and D5 has binding specificity for HER3.

17. 11. The multispecific antibody-like protein of claim 10, wherein the D1 has binding specificity for CD3, the D2 has binding specificity for CD20, the D3 has binding specificity for PD-L1, the D4 has binding specificity for 4-1BB, and the D5 has binding specificity for CD19.

18. The multispecific antibody-like protein of claim 10, wherein D1 and D6 each independently have binding specificity for a tumor associated antigen, D2 has binding specificity for CD3, D3 has binding specificity for PD-L1, and D4 has binding specificity for 4-1BB.

19. 11. The multispecific antibody-like protein of claim 10, wherein D1 has binding specificity for EGFR, D2 has binding specificity for CD3, D3 has binding specificity for PD-L1, D4 has binding specificity for 4-1BB, and D6 has binding specificity for CD19.

20. A multispecific antibody-like protein, comprising: having an N-terminus and a C-terminus, and arranged in series from the N-terminus to the C-terminus, Optionally, a first binding domain (D1) at the N-terminus, a second binding domain (D2) comprising a light chain, the light chain comprising a fifth binding domain (D5) covalently attached to the C-terminus and / or a sixth binding domain (D6) covalently attached to the N-terminus; Fc region, Optionally, a third binding domain (D3), and Optionally, a fourth binding domain (D4) at the C-terminus; Including, At least one of D1, D2, D3, D4, D5, and D6 is NKG2D; D1, D2, D3, D4, D5 and D6 are each independently a multispecific antibody-like protein that has specific binding affinity for a T cell activation receptor, an immune cell receptor, an immune checkpoint molecule, a costimulatory factor, a leukocyte receptor, a tumor antigen, a tumor-associated antigen (TAA), a tissue cell receptor, a cancer cell receptor, or a combination thereof.

21. The multispecific antibody-like protein of claim 20, wherein said D2 comprises a dimer bound to a CL and a CH1, said dimer being NKG2D.

22. 21. The multispecific antibody-like protein of claim 20, comprising an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 196 or 198.

23. 21. The multispecific antibody-like protein of claim 20, wherein a binding domain for a T-cell activating receptor is adjacent to a binding domain for a tumor-associated antigen (TAA).

24. D1, D2, D3, D4, D5, and D6 are each independently selected from EGFR, HER2, HER3, EGFRvIII, ROR1, CD3, CD28, CEA, LMP1, LMP2A, mesothelin, PSMA, EpCAM, glypican 3, gpA33, GD2, TROP2, NKG2D, NKG2D ligand, BCMA, CD19, CD20, CD33, CD123, CD22, CD30, PD-L1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, LAG 21. The multispecific antibody-like protein of claim 20, having binding specificity for an antigen selected from: IL-3, CTLA4, CD40, CD40L, VISTA, ICOS, BTLA, LIGHT, HVEM, CSF1R, CD73, CD39, CLDN18.2, DLL3, HLA-G, FcRH5, GPRC5D, LIV-1, MUC1, CD138, CD70, CD16, uPAR, Siglec-15, CD47, CD38, NKp46, PD-L2, CD160, LOX-1, SIRPα, CD27, and wherein the Fc domain comprises a human IgG Fc domain.

25. The multispecific antibody-like protein of claim 20, wherein D1, D2, D3 and D4 each independently have binding specificity for an NKG2D ligand, CD3, PD-L1, 4-1BB or a combination thereof.

26. 21. The multispecific antibody-like protein of claim 20, comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 78, 80, 82, 84, 86, 88, 30 or 32.

27. 21. An isolated nucleic acid sequence encoding the amino acid sequence of a multispecific antibody-like protein according to claim 1, 10 or 20.

28. 28. An expression vector comprising the isolated nucleic acid sequence of claim 27.

29. 29. A host cell comprising the isolated nucleic acid sequence of claim 28, The host cell is a prokaryotic or eukaryotic host cell.

30. 21. An immunoconjugate comprising a cytotoxic agent or an imaging agent attached via a linker to a multispecific antibody according to claim 1, 10 or 20, The immunoconjugate, wherein the linker comprises an ester bond, an ether bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphate ester bond, a peptide bond, a hydrophobic poly(ethylene glycol) linker, or a combination thereof.

31. A pharmaceutical composition comprising a pharma- ceutically acceptable carrier and a multispecific antibody according to claim 1, 10 or 20 and / or an immunoconjugate according to claim 30.

32. 1. A method of treating a human subject suffering from cancer, an autoimmune disease, or an infectious disease, comprising: A method comprising administering to the subject an effective amount of a multispecific antibody-like protein of claim 1, 20 or 30.

33. A solution comprising an effective concentration of a multispecific antibody-like protein according to claim 1, 20 or 30, The solution is plasma of a human subject.

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